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1
Sundelin, Kaarina. "Head and Neck Cancer : Factors Affecting Tumour Growth." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1032s.pdf.
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Murray, Patrick Francis. "Immunomodulation within the head and neck tumour microenvironment." Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:10124.
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Changes in the immune response have been implicated in the progression of squamous cell carcinoma of the head and neck (HNSCC). Evidence is emerging that processes within the tumour microenvironment can lead to immune modulation and subsequent tumour growth or metastasis. The hypothesis of this thesis is that the HNSCC tumour microenvironment will have increased levels of cytokines that produce an overall negative effect on the cellular cytotoxic immune response against the malignant cells. Specifically, it is hypothesised that a Th-2-like anti-inflammatory response will favour tumour cell progression and be associated with advanced stage HNSCC. This thesis examines the levels of a panel of immune cytokines to investigate whether difference in these levels have an association with the progression of the disease and other standard clinico-pathological factors. A method of protein extraction from tumour tissue and detection of quantitative cytokine levels was developed and optimised. A cohort of 69 patients newly-presenting with HNSCC was recruited prospectively to the study, with a total of 83 samples of primary HNSCC tumour tissue and metastatic nodal tissue being investigated. Increased levels of TGF-β, described as concentration of cytokine/mg total protein extracted, (median 1051 pg/mg vs. 659 pg/mg, p= 0.004) and reduced levels of IL-17 (median 4.2pg/mg vs. median 18.6 pg/mg, p= 0.009), compared with normal tissue from control patients were reported. The HNSCC samples were also found to have higher levels of VEGF in tumour samples (83 pg/mg vs. 27.6 pg/mg, p=0.026) compared with control tissue. No difference was found in the levels of IL-2, IL-10, IL-12, IL-15, or IL-17. When comparing early stage (I-III) to late stage IV HNSCC patients it was found that there were significantly lower levels of the Th1-like IL-12 in the higher stage IV patients (median 50pg/mg vs. 21 pg/mg, p= 0.01), and significantly higher levels of IL-15 in stage IV patients (median 52 pg/mg, vs. 20 pg/mg p= 0.03). In summary, analysis of cytokine levels within the tumour microenvironment of HNSCC may be of prognostic value, and further study of the immune suppressive nature of HNSCC could open potential therapeutic approaches, especially if such data are correlated with other cellular parameters, e.g. T regulatory or CD8+ve T cell levels.
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Kulasinghe, Arutha Jeevana. "Circulating tumour cells in head and neck cancers." Thesis, Queensland University of Technology, 2017. https://eprints.qut.edu.au/110534/1/Arutha%20Jeevana_Kulasinghe_Thesis.pdf.
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Metastasis in head and neck cancer patients is responsible for over 50% of deaths. There are currently no tools to identify patients at risk of developing metastasis. Circulating tumour cells (CTC) represent a transient cancer cell population in the blood. In this study, the researcher has developed CTC isolation methodologies and used novel culture formulations to expand patient derived CTCs for therapy testing. Furthermore, the researcher identified biomarkers present on CTCs which could select patients for immunotherapies, a current unmet need. This work sets the foundation for a personalized medicine approach to treating head and neck cancer patients.
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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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Chan, Chiu-lung Richie, and 陳肖龍. "Mucosal melanoma of the head and neck." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46632876.
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Wimardhani, Yuniardini. "Molecular Detection Of Disseminated Tumour Cells In Blood And Lymph Nodes In Patients With Head And Neck Squamous Cell Carcinoma; Correlation With Clinical And Pathological Factors And Its Effect On Patients Outcome." Thesis, The University of Sydney, 2004. http://hdl.handle.net/2123/5121.
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Zimmermann, Miriam. "The tumour microenvironment and response to therapeutic agents in head and neck squamous carcinoma cells." Thesis, University of London, 2011. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548044.
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Cheah, Ramsah. "Monitoring the response of head and neck tumour tissue to irradiation using a microfluidic-based approach." Thesis, University of Hull, 2016. http://hydra.hull.ac.uk/resources/hull:13947.
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Radiotherapy remains the standard treat74ment for head and neck squamous cell carcinoma (HNSCC), however, resistance remains a real clinical problem despite the improvements and development of new treatment strategies. Patient outcome could potentially be improved if the response to irradiation could be predicted allowing alternative treatments to be implemented. The current project has investigated the ability to maintain HNSCC tissue under pseudo in vivo-like conditions using a bespoke microfluidic device. The interrogation of the tissue with irradiation has also been performed with a view to predicting outcome and ultimately personalising medicinal treatment. Following extensive optimisation of key steps in device establishment, e.g. flow rates, serum concentration, oxygen perfusion, using rat liver and human tumour tissue, a series of HNSCC biopsies were divided and placed into parallel microfluidic devices and pieces of each tumour were subjected to single-dose irradiation (5, 10, 15, and 20Gy). Lactate dehydrogenase (LDH) release was measured in effluent collected every 2hr. In five of the tumours (primary n=3; metastatic lymph node n=2), frozen tissue sections were stained for cytokeratin (CK), M30 (detects cleaved CK-18), γH2AX, Ki-67 and for TUNEL. A CK18-labelling index (CK18-LI) was developed by expressing the percentage of apoptotic area (M30) over the total tumour area (CK+ staining). The positive γH2AX, Ki-67 expression and TUNEL were evaluated as positive nuclei within selected tumour areas. Single-dose irradiation induced variable, yet higher, CK18-LI compared with nonirradiated controls. In contrast no statistically significant differences in LDH release were observed between irradiated samples and controls. The percentage of Ki-67 expression reduced dose-dependently but not significantly following on-chip irradiation. Variation in expression profiles of these markers was identified between patients when using the same irradiation regimen demonstrating the potential of current microfluidic irradiation experimentation in monitoring patient’s radiotherapeutic response. In conclusion, microfluidics offers a potential tool in personalised medicine, capable of predicting a tumours response to irradiation prior to clinical administration although further validation experiments are required. The approach has equal applicability to all solid tumours and multiple types of treatment, i.e. chemo-radiation.
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Andrews, Nigel Anthony. "Intrinsic cellular radiosensitivity in head and neck cancer." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367189.
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Boldrup, Linda. "p63 and potential p63 targets in squamous cell carcinoma of the head and neck." Doctoral thesis, Umeå : Univ, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1522.
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Hunter, Keith David. "Gene expression analysis of head and neck cancer development." Thesis, University of Glasgow, 2005. http://theses.gla.ac.uk/1712/.
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Microarray analysis was performed on 32 head and neck keratinocytes cultures using Affymetrix U133A/B genechips. The panel of cultures included normal cells, mortal and immortal cultures of dysplastic keratinocytes and mortal and immortal cultures from carcinomas, all grown to a standard protocol. The overall GEP revealed that many of the well-established HNSCC molecular markers associated with motility and invasion were up-regulated in the mortal cells, particularly in the mortal carcinomas. Immortal NHSCC cells showed elevated expression of cell-cycle markers and loss of differentiation markers. In addition, a small number of common changes in gene expression in all the carcinomas, regardless of replicative fate, were identified. This included several transcription factors. A series of 49 novel gene expression changes consistently associated with immortality in dysplastic keratinocytes and SCCs were identified. The list included genes involves in cell cycle control, signalling, cellular metabolism and maintenance of cellular structure. Validation of the expression of these genes by western blot demonstrated that, in general, the protein expression of genes agreed with the RNA expression level from the microarray data. However, some heterogeneity was evident. The mortal and immortal gene expression signatures were validated by IHC in the tumours from which the cultures were derived. The tumours that gave rise to immortal cell cultures demonstrated a relatively uniform pattern of staining in relation to the novel markers of immortality. However, those tumours which gave rise to mortal cultures exhibited significant heterogeneity of gene expression pattern, with areas characteristic of both the mortal and immortal phenotype present. These novel markers give us further insight into the mechanisms and importance of keratinocytes immortalization. Surrogate markers of immortality could therefore be valuable for assessment of prognosis and therapy if confirmed in larger in vivo studies.
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Modasia, Bhavika. "PTTG, PBF and p53 in head and neck cancer." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7574/.
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Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and poses a significant health burden due to its rising incidence. The proto-oncogene PTTG is overexpressed in HNSCC and correlates with poor patient prognosis. A recent unpublished GEO profile eDNA array analysis has further suggested a potential upregulation of its binding partner PBF in HNSCC. PTTG and PBF cause transformation in vitro and tumour formation in vivo, both effects thought to be partly mediated by their interactions with the tumour suppressor protein p53. Dysregulation of the p53 pathway is frequently observed in HNSCC, thus alluding to the importance of functionally active p53 in the suppression of HNSCC initiation and progression. The work presented in this thesis describes the functional relationship between PTTG, PBF and p53 in HNSCC. Initial studies confirmed that PTTG and PBF are overexpressed in HNSCC tumours compared to matched normal tissue. In addition, high tumoural PTTG expression correlated with HPV status, whereas high tumoural PBF expression was associated with a significant gender bias. Further investigations established that PTTG and PBF functionally interact with p53 and cooperate to reduce p53 protein stability in HNSCC cells. Moreover, attenuation of PTTG or PBF expression led to dysregulated expression of p53-related genes involved in DNA repair and apoptosis, indicating that both proto-oncogenes may serve to promote genomic instability and HNSCC cell survival. Functionally, depletion of PTTG or PBF significantly repressed cellular migration and invasion, and impaired colony formation in HNSCC cells. Overall, this research has provided novel insights into the roles of PTTG and PBF in HNSCC tumour initiation and progression, through modulation of p53 activity and function.
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Nordemar, Sushma. "Methods for early diagnosis of head and neck cancer /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-872-6/.
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Viblom, Jonathan, and Jonas Emauelsson. "Mandibular Reconstruction after Head and Neck Tumor Treatment, a Systematic Review." Thesis, Umeå universitet, Institutionen för odontologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-97844.
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Objectives This systematic literature review examined the literature about mandibular reconstruction after cancer treatment with segmental resection, with focus on success rate for the reconstruction, patient survival rate, dental rehabilitation and how this effect the patients QOL, oral function and aesthetics. Material and methods A search was performed in Pubmed, a database of scientific articles, based on four keywords (Mandibular, Reconstruction, Cancer, Segmental). After screening using our inclusion and exclusion criteria’s, 89 articles were chosen. A data base in excel was established to sort the information we needed for our study. Results Sixty out of the 89 included articles were in full text and 29 were abstracts. The median year of publication was 2006 (range 1977 to 2013). A total of 5629 patients were included in the literature review. Of these, 3783 patients were included in articles that had categorized by gender and we found that 65.4% were males and 34.6% were females. The total success rate for reconstruction therapies including plate, vascularized- and non-vascularized bone transplant was 86.4% in 3219 patients (range from 70.4% in the plate group to 92.3% in the non-vascular group). The mean follow up time were 46.9 mounts (range 0.2 – 216 months). Conclusion This literature review indicates a focus on success rates for different kinds of reconstruction techniques. The overall success rate for non- and vascularized bone reconstruction techniques were very high compared to plate reconstruction only. To evaluate patient-related factors such as function, aesthetics and quality of life, further prospective randomized studies is required.
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Wilkie, Mark David. "Tumour metabolism in squamous cell carcinoma of the head & neck : consequences & potential therapeutic implications of TP53 mutation." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3021106/.
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Survival outcomes for traditional Human papillomavirus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN) have not improved significantly over the last 20-30 years. In contrast, HPV-positive oropharyngeal SCC is associated with favourable survival outcomes, but patients often suffer long-term functional ramifications from the toxicity of their treatment. Therefore, in the context of HPV-negative SCCHN there is a need to improve treatment efficacy to enhance survival outcomes, while for HPVpositive oropharyngeal SCC there is a need to minimise treatment-associated toxicity. Fundamental to this is to identify novel radiosensitising therapeutic approaches given that radiotherapy (RT) remains a mainstay of treatment for all SCCHN patients. Cancer cell metabolism is an attractive putative target in this regard, yet has received relatively little attention in the context of SCCHN. p53 is known to be a potentially important metabolic mediator, while TP53 mutation is central to SCCHN oncogenesis and is associated with poorer clinical outcomes. Consequently, the primary of aims of thesis these were to examine the metabolic phenotype exhibited by SCCHNs, whether this was related to TP53 status, and to determine whether tailored anti-metabolic treatment might have potential therapeutic value, specifically in enhancing the effects of ionising radiation (IR). Secondary aims were to explore the mechanistic basis underlying any metabolic alterations and any observed anti-metabolic therapeutic effects. Microplate-based extra-cellular flux analysis revealed that mutant TP53 SCCHN cell lines exhibited a distinct metabolic phenotype to that of wild-type TP53 cell lines. Wildtype TP53 cells maintained metabolic diversity, while mutant TP53 cells exhibited a specific survival dependence on glycolysis. This correlated with radiation response following glycolytic inhibition with 2-deoxy-D-glucose (2-DG), which potentiated IR effects in mutant TP53 cells only. In line with their more diverse metabolic phenotype, in wild-type TP53 cells (HPV-positive SCCHN cells included) a broader anti-metabolic approach, comprising both 2-DG and metformin (inhibitor of mitochondrial respiration), was required to achieve a similar effect. The potentiating effects of glycolytic inhibition on IR in mutant TP53 SCCHN cells were reversed by the addition of N-acetylcysteine (free radical scavenger). Consistent with this, flow cytometry demonstrated a marked increase in reactive oxygen species (ROS) following IR + 2-DG, and also increased levels of apoptosis, implicating oxidative stress-mediated activation of apoptotic signalling as the mechanism underlying the radiosensitising effects of 2-DG. That oxidative stress was centrally involved in the mechanism underlying glycolytic inhibition in SCCHN also suggested that the impetus driving mutant TP53 SCCHN cells towards glycolysis was at least partly to regulate cellular redox status and evade excessive ROS accumulation. In accordance with this, pentose phosphate pathway (PPP) enzyme expression and intracellular NADPH/NADP ratios were greater in mutant TP53 SCCHN cells, indicative of increased PPP flux. This appeared to be mediated by de-regulated TIGAR overexpression in those cells with loss of p53 function. Therapeutically, the addition of the PPP inhibitor 6-aminonicotinamide further potentiated IR effects in mutant TP53 cells over and above glycolytic inhibition. Ultimately, the findings described in this thesis present the opportunity for a novel, tailored anti-metabolic therapeutic approach in SCCHN, which not only carries a selective therapeutic index, but is also informed by TP53 status as a predictive biomarker. Specifically, we propose that in mutant TP53 SCCHNs glycolytic inhibition with 2-DG, possibly in combination with 6-AN-induced PPP inhibition, would result in significant radiosensitisation. This strategy would be applicable in upwards of 60-85% of SCCHN tumours and would be preferentially effective in targeting the treatmentresistant disease typically associated with TP53 mutation. For SCCHNs harbouring wildtype TP53 (HPV-positive disease included) we suggest the combination of 2-DG with metformin. This strategy may also provide an attractive platform for the treatment deintensification of carefully selected HPV-positive cases by facilitating RT dose reduction to minimise the impact of treatment on long-term function. The efficacy and safety of these strategies will require further validation in pre-clinical models prior to translation into the clinical setting, and future work will be directed in this regard.
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Moutasim, Karwan A. "Integrin avb6 : expression and function in head and neck cancer." Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/374708/.
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Nestor, Marika. "Antibody-Based Radionuclide Targeting for Diagnostics and Therapy : Preclinical Studies on Head and Neck Cancer." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7341.
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Markkola, Antti. "Spin lock and magnetization transfer imaging of head and neck tumors." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/markkola/.
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Cheng, Junping. "Radioimmunotherapy in Experimental Head and Neck Squamous Cell Carcinoma : Tumour-targeting in vitro and in vivo." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5834.
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Snaddon, Jennifer A. M. "Molecular analysis of the tumour suppressor genes MXI1 and PTEN in human squamous cell carcinoma of the head and neck." Thesis, Glasgow Caledonian University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340609.
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Sylvester, Deborah Claire. "Development of micro fluidic based devices for studying tumour biology and evaluating treatment response in head and neck cancer biopsies." Thesis, University of Hull, 2011. http://hydra.hull.ac.uk/resources/hull:7087.
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Head and Neck Squamous Cell Carcinoma (HNSCC) presents particular challenges to both the researcher and the clinician. Encompassing a group of tumours with distinct epidemiological and oncological behaviour, each sub site differs greatly in its management and prognosis. However, due to insufficient tissue quantities and culture techniques, research studies commonly group together different sub sites, limiting our understanding of the biological behaviour and treatment response of tumours from distinct sites. Micro fluidics relates to the science of systems that process or manipulate small amounts of fluids within micro channels. When applied in biology, the technology enables the production of simple, robust and highly versatile systems for studying cells and tissues. The aim of the work in this thesis was to maintain small biopsies of tumour in a physiological state, more comparable to the in vivo environment than traditional tissue culture techniques, for up to 9 days. This recreation of the ‘tumour microenvironment’ in vitro provided a platform for the testing of chemotherapy agents and analysing individual tumour behaviour. Initial optimisation studies were performed to demonstrate tissue viability within this novel culture method. Based on LDH excretion as a marker of cell death and WST-1 metabolism as a marker of viability, tumour and nodal biopsies from a variety of sub sites remained viable within the device until the addition of cell lysis buffer at 68 h. Histo-architectural examination of tissue incubated within the device for 96 h demonstrated that original tissue structure is largely maintained. In addition, comparison of viability between fresh and frozen tissues showed little difference, thus the clinical applicability of the technique was significantly enhanced, as biopsies could be collected and stored prior to use at a later date. Using clinically relevant combinations of chemotherapy drugs, nodal biopsies (n=50 micro chips from n=2 tumours with all experiments duplicated) were interrogated with cisplatin, 5-Fluorouracil and docetaxel within the micro device for up to 9 days. The addition of each chemotherapeutic agent resulted in increased cell death compared to control, with a synergistic effect seen when agents were given in combination; results in agreement with clinical trial data. This study demonstrates a robust and reproducible system for the maintenance and ‘interrogation’ of individual tumour biopsies. The innovative model provides a new platform for testing individual patient responses to chemotherapy, paving the way for ‘personalised’ treatment regimens.
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Recalde-Percaz, Leire. "Neuropilin 2 role in the regulation of disseminated tumour cells dormancy and metastasis in breast and head and neck cancer." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/672374.
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Metastases are considered the last stage of tumour progression and the main cause of death associated to solid tumours. There are no effective treatments for metastasis which remain non- curable with more than 90% of patients dying from metastatic disease. They derive from disseminated tumour cells (DTCs) that can remain occult in a dormant state while adapting to the new microenvironment. By mechanisms that are still unclear, dormant DTCs can re-activate and become proliferative giving rise to metastatic outgrowth. Therefore, understanding the mechanisms by which metastases are formed is essential to face one of the most important problems in clinical oncology. Metastasis development depends on DTCs survival in circulation as well as on their ability to colonize new microenvironments. Therefore, we propose that the tumour microenvironment regulates the fate and survival of DTCs in secondary organs, hence regulating metastases.
This project has been developed in order to decipher the role of the nervous system in breast cancer (BrCa) and head and neck cancer (HNSCC) progression and metastasis. Particularly, we have investigated whether the neurogene neuropilin 2 (NRP2) has a crucial role in regulating DTCs biology and in remodelling the metastatic niche generating a favourable microenvironment for the survival and proliferation of the DTCs, all stimulating metastasis. As classical partners of NRPs, we have also studied the effect of class 3 semaphorins (SEMA3s) and their receptors, plexins (PLXNs), on tumour cells biology.
On one hand, we have shown that SEMA3F has an anti-tumour effect in vivo increasing quiescence markers expression and inducing a switch in primary tumours behaviour to a more dormant phenotype. We have also shown that it diminishes cell dissemination to secondary organs, which makes SEMA3F a potential good prognosis factor in BrCa and HNSCC. On the other hand, our results suggest that PLXNA2 inhibits tumour growth as well as prevents cell migration and invasion while it might modulate cell stemness. Moreover, we have also found that PLXNA3 might restrain tumour growth in oestrogen receptor (ER)-positive breast tumours and that the oestrogen signalling up- regulates PLXNA3 expression, associating PLXNA3 with longer dormancy periods of ER-positive breast tumours.
Finally, we have mainly focused on deciphering the role of NRP2 in regulating DTCs biology and lung metastases. Here, we have shown that NRP2 positively regulates BrCa and HNSCC cells proliferation, adhesion, migration, invasion and survival in vitro and in vivo. NRP2 deletion clearly inhibits tumour growth in vivo as well as decreases the number and size of lung metastases. Moreover, NRP2 is essential for lung DTCs proliferative phenotype, hence promoting lung metastases growth in vivo. Highlighting the role of the microenvironment, we have shown that the lung microenvironment up- regulates NRP2 expression partly by macrophages and fibroblasts-derived TGFβ1. Altogether, this thesis contributes to a better understanding of DTCs biology describing TGFβ1-NRP2 axis as a dormancy inhibitor pathway, promoting DTCs re-awakening and lung metastases development. The negative correlation of NRP2 expression with metastasis free survival in BrCa and HNSCC patients’ and our results emphasizing the metastatic role of NRP2, suggest that NRP2 could be a bad prognosis biomarker and a good target to design new drugs against metastasis.<br>Les metàstasis, principal causa de mortalitat associada a tumors sòlids que provoquen la mort de més del 90% dels pacients, no disposen d’un tractament efectiu. Les metàstasis deriven de cèl·lules tumorals disseminades (CTDs) que escapen del tumor primari i, després d’un període d’adaptació al nou microambient, proliferen donant lloc a la metàstasi. Durant aquest període d’adaptació, les CTDs entren en un estat de latència que es caracteritza per una parada del cicle cel·lular, fet que les fa invisibles davant de les teràpies actuals. Mitjançant mecanismes parcialment desconeguts, les CTDs es reactiven i proliferen generant la metàstasi. Per tant, és imprescindible millorar el coneixement sobre la biologia de les CTDs per fer front a un dels principals problemes de l’oncologia clínica actual. Per tal que es generi una metàstasi, es requereix la supervivència de les CTDs tant en circulació com al nou microambient que colonitzaran. Tenint tot això en compte, proposem que el microambient tumoral influencia el fenotip i la supervivència de les CTDs, regulant així la formació de metàstasis.
Aquesta tesi ha tingut com a objectiu l’estudi de la influència de factors neuronals en el desenvolupament del tumor i la metàstasi als càncers de mama i de cap i coll. Concretament, hem estudiat el paper de la Neuropilina 2 (NRP2) en la regulació de la biologia i supervivència de les CTDs, així com en la modulació del microambient tumoral, afavorint la formació de metàstasis. Així mateix, hem analitzat l’efecte i la contribució de les semaforines de classe 3 (SEMA3s) i els seus receptors, les plexines (PLXNs), als càncers de mama i de cap i coll.
D’una banda, hem posat de manifest la funció anti-tumoral de la SEMA3F en augmentar l’expressió de marcadors de latència, a més de reduir la disseminació tumoral i d’induir fenotips menys proliferatius a les CTDs in vivo. D’altra banda, els nostres resultats suggereixen que la PLXNA2 semblaria inhibir el creixement de tumors de mama receptor d’estrogen (ER)-negatius, disminuint la migració i invasió cel·lular. Altrament, l’expressió de la PLXNA3 està regulada per la via dels estrògens, associant la seva expressió als períodes de latència més perllongats en tumors de mama ER-positius. Finalment, el nostre estudi s’ha centrat a determinar la funció de la NRP2 a les CTDs i al desenvolupament de metàstasis al pulmó. En concret, hem demostrat la relació de l’expressió de NRP2 amb una major proliferació, adhesió, migració, invasió i supervivència cel·lular in vitro i in vivo. En concordança, hem mostrat que la inhibició de NRP2 redueix tant el creixement del tumor primari com la formació de metàstasis als pulmons in vivo. Finalment, destacant el paper del microambient tumoral als pulmons, hem vist que el TGFβ1 secretat pels macròfags i fibroblasts pulmonars augmenta l’expressió de NRP2 a les cèl·lules tumorals.
En definitiva, aquesta tesi contribueix a un major coneixement de les CTDs descrivint l’eix TGFβ1- NRP2 com a inhibidor de la latència cel·lular i promotor de les metàstasis pulmonars. Tenint en compte la correlació de l’expressió de NRP2 en pacients de càncer de mama i de cap i coll amb una major incidència de metàstasis, definim la NRP2 com a marcador de mala prognosi contra la qual generar possibles noves eines terapèutiques per a millorar els tractaments de la malaltia metastàtica
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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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Marcu, Loredana Gabriela. "Deterministic modelling of kinetics and radiobiology of radiation-cisplatin interaction in the treatment of head and neck cancers." Title page, contents and abstract only, 2004. http://hdl.handle.net/2440/37961.
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One of the main objectives of combining radiation treatment and chemotherapy is to obtain a therapeutic gain by an improved tumour control with less or no enhancement of normal tissue toxicity. The optimal schedule for the combined treatment of cisplatin-radiation is still under investigation. Neither the optimal time interval, nor the most adequate sequence of administration of cisplatin and radiation are known. The results of the trials are also inconclusive. Some trials showed a supra-additive effect from the administration of cisplatin before radiotherapy, others, on contrary, from the injection of drug after radiotherapy. The present work encompasses the major challenges brought by the combined modality treatment: cisplatin-radiotherapy. The major goal of this work was to investigate the optimal treatment sequencing between cisplatin and radiotherapy and also the optimal schedule for head and neck carcinomas. Therefore, a computer-based tumour model with literature-given biological parameters has been developed which has allowed the simulation of treatment with radiation and chemotherapy. Radiotherapy has been simulated on the virtual tumour and the effects of radiotherapy on tumour regression and regrowth have been analyzed. Also, the mechanisms of cisplatin's action on tumour have been implemented, and the phenomena of drug resistance and tumour repopulation during chemotherapy studied. Finally, the combined modality treatment has been simulated, and the effect of drug-radiation interaction on tumour behaviour evaluated. The current investigation has shown that cisplatin administered immediately before radiation gives similar tumour control to the post-radiation sequencing of the drug. Furthermore, the killing effect of the combined modality treatment on tumour increases with the increase in cell recruitment. The individual cell kill produced by cisplatin and radiation leads to an additive-only tumour response when the treatments are given concurrently, and for a synergistic effect cisplatin must potentiate the effect of radiation. The final conclusion, by which cisplatin administered on a daily basis leads to a better tumour control than cisplatin administered weekly, is in accordance with the latest trial results on head and neck cancers. Therefore, treatment regimens that correlate better with the pharmacokinetics and the radiobiological properties of the therapeutic agents result in better outcomes.<br>Thesis (Ph.D.)--School of Chemistry and Physics, 2004.
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Haylock, Anna-Karin. "Targeting molecules for diagnostics of Head and Neck squamous cell carcinoma." Doctoral thesis, Uppsala universitet, Öron-, näs- och halssjukdomar, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-315210.
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To personalize treatment for cancer, correct staging of the primary tumor, nodal disease and metastatic disease is of essence. By targeting tumor specific receptors with radiolabeled antibodies, specificity and accuracy of imaging may be improved. Radio-immunodiagnostics can potentially detect small volume disease, occult metastasis and recurrent cancer in treated tissue. This thesis focuses on evaluation of radio-immunoconjugates directed towards CD44v6, which is a surface receptor overexpressed in many head and neck squamous cell carcinomas. At the outset, the monoclonal chimeric antibody cMab U36 and its cleavage products Fab’ and F(ab’)2 were labeled with 125I and assessed in vitro and in vivo (paper I). The best distribution pattern and tumor to organ ratio was achieved with F(ab’)2. Due to the immunological responses humans can develop towards chimeric antibodies, they are not optimal for clinical use, and subsequently fully human antibody fragments were developed. AbD15179, which is a monovalent fragment, was labeled with 111In and 125I and evaluated in vitro and in mice bearing CD44v6-expressing tumors. Tumor to organ ratios were improved compared to cMab U36 derived fragments, and 111In-AbD15179 displayed a more favorable distribution compared to 125I-AbD15179 (Paper II). A bivalent Fab-dHXL, AbD19384 derived from AbD15179, was then constructed and labeled with 125I and evaluated in cell- and biodistribution studies. Furthermore, an imaging study in a small animal PET was performed with 124I-AbD19384 (Paper III). Uptake in kidneys was reduced and liver uptake increased compared to AbD15179 reflecting the larger molecule. The high CD44v6 expressing tumor was clearly visualized with maximum uptake at 48 hours post injection.In paper IV human single chain fragments towards CD44v6v were selected, and the top candidates A11 and H12 were further evaluated in vitro and in vivo. Single chain fragments are small molecules exhibiting fast clearance and high affinity to the target. The study proved this by demonstrating superior tumor to blood ratios of radiolabeled A11 and H12 compared to previously studied molecules.
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Ekberg, Tomas. "Diagnosis and Radioimmunotherapy of Head and Neck Squamous Cell Carcinomas." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8395.
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Nutting, Christopher. "Can intensity-modulated radiotherapy (IMRT) be used to reduce toxicity and improve tumour control in patients with head and neck cancer?" Thesis, City University London, 2012. http://openaccess.city.ac.uk/1128/.
Texte intégralRésumé :
Radiotherapy is commonly used in the treatment of head and neck cancer. For early stage tumours, conventional radiotherapy techniques have a high cure rate and low levels of long-term complications. Patients with more advanced cancers have much lower cure rates and high levels of treatment-related complications. Intensity modulated radiotherapy (IMRT) is a new form of focussed radiation therapy. It has been used to reduce the radiation dose to normal tissue structures and increase the dose delivered to tumour bearing tissues. This potentially allows reduced side effects and increased tumour control compared to conventional radiotherapy. The rationale of this thesis was to test whether these twin goals could be achieved in head and neck cancer patients. The first part of the thesis describes improvements in patient immobilisation, optimisation of techniques for neck irradiation, and evaluation of the technique in a busy radiotherapy department. It includes pre-clinical evaluation of IMRT for different tumour sites, the development of quality assurance programs and the conduct of a national randomised controlled trial of parotid-sparing IMRT. This trial concluded that IMRT significantly reduced patient-reported xerostomia, allowed recovery of saliva production and improved quality of life. The second part of the thesis describes pre-clinical evaluation of techniques to escalate radiation dose in patients with larynx and hypopharynx tumours. A phase I/II clinical trial showed that higher doses of radiation can be delivered at the expense of an increase in acute radiation toxicity but without a measurable increase in late radiation side effects. In the larynx and hypopharynx groups, a possible increase in local control was observed. This thesis describes the process of evaluation of a new radiotherapy technology and could be used as a template for testing other new technologies in the future.
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Lundmark, Martin. "Clinical evaluation of atlas-based segmentation for radiotherapy of head and neck tumours." Thesis, Umeå universitet, Institutionen för fysik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-45571.
Texte intégralRésumé :
Background Semi-automated segmentation using deformable registration of atlases consisting of pre-segmented patient images can facilitate the tedious task of delineating structures and organs in patients subjected to radiotherapy planning. However, a generic atlas based on a single patient may not function well enough due to the anatomical variation between patients. Fusion of segmentation proposals from multiple atlases has the potential to provide a better segmentation due to a more complete representation of the anatomical variation. Purpose The main goal of the study was to investigate potential operator timesaving from editing of atlas-based segmentation compared to manual segmentation for head & neck cancer. Materials and Methods A commercial atlas-based segmentation software (VelocityAI from Nucletron AB) was used together with several expert generated and protocol-based atlases of delineated CT images to create multiple atlas segmentations through deformable registration. The atlas that was considered most universal was selected to construct single atlas segmentation proposals. For fusion of the multiple atlas segmentations an in-house developed algorithm, including information of local registration success was used in a MATLAB-environment1. The algorithm uses weighted distance map calculations where weights represent probabilities of improving the segmentation results. Based on previous results1 the probabilities were estimated using the cross correlation image similarity measure evaluated over a region within a certain distance from the segmentation. Ten patients were incorporated in the study. Each patient was delineated three times, (a) manually by the radiation oncologist, (b) with a single atlas segmentation and (c) with a fusion of multiple atlas segmentations. For the methods (b) and (c) the radiation oncologist corrected the proposed segmentations blindly without using the result from method (a) as reference. For case (c) a total number of 11 atlas segmentations were used. The time spent for segmenting or editing the segmentation proposals by the radiation oncologist was recorded separately for each method and each individual ROI. In addition a grading was used to score how helpful the candidate segmentation proposals were for the structure delineations. The Dice Similarity Coefficient, the Hausdorff distance and the volume were used to evaluate the similarity between the delineated structures. Results The results show a time reduction in the order of 40% when the radiation oncologist only has to correct the multiple atlas-based segmentation proposal compared to manual segmentation. When using single atlas the corresponding figure is 21%. Conclusions Using atlas-based segmentation can reduce the time needed for delineation in the head and neck area of patients admitted for radiotherapy. 1C. Sjöberg and A. Ahnesjö, Evaluation of atlas-based segmentation using probabilistic weighted distance maps, Manuscript, Uppsala University, 2011<br>Bakgrund Atlasbaserad, semiautomatisk segmentering skulle kunna användas för att underlätta den för onkologen tidskrävande uppgiften med att manuellt segmentera strukturer och organ i patienter vid behandlingsplanering inför strålbehandling. Tidigare segmenterade atlaspatienter ger med hjälp av deformeringsalgoritmer segmenteringsförslag för strukturer i den aktuella patienten. Dessa kan sedan kontrolleras och editeras av onkologen med en tidsbesparing gentemot manuell segmentering som följd. En atlas som baserats på en enstaka individ (singelatlas) kan dock ha begränsningar när det gäller att täcka de anatomiska variationer som finns mellan olika patienter. Därför har metoder med fusionering av multipla segmenteringsförslag från en databas bestående av ett antal sedan tidigare segmenterade patienter (fusionerad multipelatlas) potential att ge ett bättre segmenteringsresultat. Syfte Huvudsyftet med arbetet var att undersöka de möjliga tidsbesparingar för onkologen som kan åstadkommas när editering av atlasbaserad segmentering används vid planering inför strålbehandling i huvud- och halsområdet istället för manuell segmentering Material och metoder En kommersiell, atlasbaserad segmenteringsprogramvara (VelocityAI från Nucletron AB) användes i studien. Genom att låta en erfaren onkolog segmentera ett antal CT-studier (11 st) enligt ett vedertaget protokoll skapades en databas av atlaser som sedan, via deformerbara registreringar, kunde generera lika många segmenteringsförslag för en nytillkommen patient. Den enskilda atlas som ansågs mest representativ valdes till att framställa segmenteringsförslaget för metoden med singelatlas. Till metoden med fusionerade multipla atlaser användes en lokalt utvecklad MATLAB-algoritm baserad på viktade distansmappar. Vikterna representerar sannolikheten för förbättrat segmenteringsresultat och baseras på tidigare resultat1 där sannolikheterna bestämts utifrån en beräkning av likheterna mellan bilderna i ett visst område från den specifika segmenteringen. Tio patienter har inkluderats i studien. Varje patient segmenterades tre gånger, (a) manuellt, (b) med singelatlas och (c) med fusionerade multipla atlaser. För metoderna (b) och (c) editerades sedan segmenteringsförslagen av onkologen utan att denne fick använda resultatet från metod (a) som referens. För fallet med fusionerade multipla atlaser, (c), användes databasen med 11 atlaser. Tiden onkologen behövde för segmentering respektive editering av segmenteringsförslaget uppmättes i varje enskilt fall för jämförelse. Onkologen fick även göra en bedömning av hur hjälpsamt segmenteringsförslaget var i samband med editeringen. För utvärdering av resultaten användes Dice’s similaritetskoefficient, Hausdorff’s distansmått samt strukturernas volym. Resultat Resultaten visar på att en tidsbesparing i storleksordningen 40 % är rimlig när onkologen editerar förslag från fusioneringen av multipla atlassegmenteringar i jämförelse med manuell segmentering. Vid användning av singelatlas är motsvarande siffra 21 %. Slutsatser Användandet av atlasbaserad segmentering kan reducera tidsåtgången för segmentering av patienter inför strålbehandling i huvud-halsområdet. 1C. Sjöberg and A. Ahnesjö, Evaluation of atlas-based segmentation using probabilistic weighted distance maps, Manuscript, Uppsala University, 2011
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MISSALE, FRANCESCO. "Immune contexture monitoring in solid tumors focusing on Head and Neck Cancer." Doctoral thesis, Università degli studi di Brescia, 2023. https://hdl.handle.net/11379/570176.
Texte intégralRésumé :
Forti evidenze dimostrano una stretta interazione tra il sistema immunitario e lo sviluppo biologico e la progressione clinica dei tumori solidi. L'effetto che il microambiente immunitario del tumore può avere sul comportamento clinico della malattia è indicato come "immunecontexture". Nonostante ciò, l'attuale gestione clinica dei pazienti affetti da cancro non tiene conto di alcuna caratteristica immunologica né per la stadiazione né per le scelte terapeutiche. Il tumore della testa e del collo (HNSCC) rappresenta il 7° tumore più comune al mondo ed è caratterizzato da una prognosi relativamente sfavorevole e dall'effetto negativo dei trattamenti sulla qualità della vita dei pazienti. Oltre alla chirurgia e alla radioterapia, sono disponibili pochi trattamenti sistemici, rappresentati principalmente dalla chemioterapia a base di platino-derivati o dal cetuximab. L'immunoterapia è una nuova strategia terapeutica ancora limitata al setting palliativo (malattia ricorrente non resecabile o metastatica). La ricerca di nuovi biomarcatori o possibili nuovi meccanismi target è molto rilevante quindi nel contesto clinico dell'HNSCC. In questa tesi ci si concentrerà sullo studio di tre possibili popolazioni immunitarie pro-tumorali studiate nell'HNSCC: i neutrofili tumore-associati (TAN), le cellule B intratumorali con fenotipo immunosoppressivo e i T-reg CD8+. Particolare attenzione è data all'applicazione di moderne tecniche biostatistiche e bioinformatiche per riassumere informazioni complesse derivate da variabili cliniche e immunologiche multiparametriche e per validare risultati derivati in situ, attraverso dati di espressione genica derivati da dataset pubblici. Infine, la seconda parte della tesi prenderà in considerazione progetti di ricerca clinica rilevanti, volti a migliorare l'oncologia di precisione nell'HNSCC, sviluppando modelli predittivi di sopravvivenza, confrontando procedure oncologiche alternative, validando nuovi classificatori o testando l'uso di nuovi protocolli clinici come l'uso dell'immunonutrizione.<br>Strong evidences demonstrate a close interplay between the immune system and the biological development and clinical progression of solid tumors. The effect that the tumor immune microenvironment can have on the clinical behavior of the disease is referred as the immuno contexture. Nevertheless, the current clinical management of patients affected by cancer does not take into account any immunological features either for the staging or for the treatment choices. Head and Neck Cancer (HNSCC) represents the 7th most common cancer worldwide and it is characterized by a relatively poor prognosis and detrimental effect of treatments on the quality of life of patients. Beyond surgery and radiotherapy, few systemic treatments are available, mainly represented by platinum-based chemotherapy or cetuximab. Immunotherapy is a new therapeutical strategy still limited to the palliative setting (recurrent not resectable or metastatic disease). The search for new biomarkers or possible new targetable mechanisms is meaningful especially in the clinical setting of HNSCC. In this thesis a focus will be given on the study of three possible pro-tumoral immune populations studied in HNSCC: the tumor associated neutrophils (TAN), intratumoral B-cells with a immunosuppressive phenotype and the CD8+ T-regs. Biostatistical and bioinformatical techniques are applied to summarize complex information derived from multiparametric clinical and immunological variables and to validate in-situ derived findings through gene expression data of public available datasets. Lastly, the second part of the thesis will take into account relevant clinical research projects, aimed at improving the precision oncology in HNSCC developing survival prediction models, comparing alternative oncological procedures, validating new classifiers or testing the use of novel clinical protocols as the use of immunnutrition.
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Reid, Katherine Jane. "The experience of patients diagnosed and treated for head and neck cancer." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4333/.
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Head and neck cancer (H&NC) and its possible treatment options are diverse and multifaceted. This thesis demonstrates these complexities and describes three studies that have used different methodological approaches to include, rather than overlook these aspects. The first established which aspects of patients’ experiences are overlooked if health care professionals rely upon health related quality of life questionnaires to represent the experience of patients. The second identified that the multi-disciplinary team (MDT) working with the patients use humane judgement, not technical expertise, to predict patients’ symptoms pre treatment. The third, with reference to the previous two, used Q-Methodology to explore the experience of H&NC patients during and after their treatment. Five interpretations were identified: • Meaning and attachment to illness • Overwhelmed by the disease • Change and recovery • Surviving or not • Keep control- for the greater good of others This unique study has developed a framework through which the MDT can start to translate H&NC patients’ experiences and help enable them to influence their care directly. It also suggests ways in which the framework can be applied to the clinical environment.
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Forootan, Shiva Seyed. "Neoangiogenesis in squamous cell carcinoma of head and neck in relation to basic fibroblast growth factor." Thesis, University of Liverpool, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367196.
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McCaul, James A. "Telomere function and the radiosensitivity of squamous carcinoma of the head and neck." Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/4117/.
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This thesis considers whether the alteration of telomere function by manipulation of the telomerase enzyme can affect the radiosensitivity of in vivo derived SCCHN cells and hence whether telomere dysfunction inducing strategies are likely to be synergistic with ionising radiation in the management of SCCHN. The role of telomerase in radioprotecting cancer cells is investigated using the ectopic expression of hTERT in cell lines with high and low levels of telomerase. The effect of inhibiting telomerase expression is examined using a dominant negative telomerase gene. This approach had little success in SCCHN cells and so further experiments designed to elaborate the effect of telomerase inhibition on radiosensitivity were carried out using the small molecule reverse transcriptase inhibitor 3’ – azido, 3’ – deoxythymidine (AZT). These showed both telomerase suppression and increased radiosensitivity in cells exposed to AZT in culture. Other suggested factors which may affect the success of radiotherapy for cancer include the missense mutation of the p53 gene. A common polymorphism at codon 72 gives rise to Arginine or proline forms of the protein. This thesis investigates whether this variation affects radiosensitivity in SCCHN cells by assessing a panel of in vivo derived SCCHN cell lines. If the level of telomerase expression does not impact on radiosensitivity, then the use of antitelomerase strategies may be less effective with higher levels of telomerase expression in tumours. Continued selective pressure during tumour progression may mean the emergence of clonal variants with improved telomere function via greater levels of telomerase. This is investigated by anaphase bridge scoring of primary and recurrent archival tumour material. Analysis of cells from primary lesions and then from recurrent disease in the same patient provides information in this regard.
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Lara, Ana. "FDG tumor volumetric parameters and outcome in lung cancer and head and neck cancer." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12464.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.<br>Lung cancer (LC) is the leading cause of cancer mortality worldwide and second most common type of cancer in the United States in both genders. Moreover, Head and neck cancer (HNC) is the sixth most common cancer worldwide and 4% of all malignancies in the United States. The role of FDG-PET-CT has recently increased in oncology for diagnosis, treatment monitoring and patient prognosis. FDG Metabolic parameters sued to assess patient care include maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and total glycolytic activity. This study attempts to prove FDG-metabolic parameters reliability in LC and HNC patients before and after treatment among readers with different levels of experience. Three readers, 2 experienced and 1 inexperienced, read before and after treatment scans of 74 FDG-PET-CT scans from 13 lung cancer patients and 24 head and neck cancer patients. Lesion location was provided beforehand and reliability was tested using intra-class correlation coefficients (ICC) and ANOVA analysis. For every case, ICC was >0.81 (almost perfect agreement) among all readers and ANOVA showed no statistical significance (p>0.05) on the any of the measurements among all readers as well. We concluded that FDG-PET-CT metabolic parameters (SUVmax, MTV, and TGA) are reliable measurements for treatment response in LC and HNC patients and are independent of reader experience as long as lesion location is provided. These parameters have been found to accurately correlate with tumor behavior and patient prognosis; therefore, reliability on its accurate measurement provides strength to FDG-PET-CT as an imaging modality of choice for oncology patients.
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Baboci, Lorena. "Human papillomavirus - associated head and neck squamous cell carcinomas in North-East Italy." Doctoral thesis, Università degli studi di Padova, 2014. http://hdl.handle.net/11577/3423688.
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Background: Specific oncogenic types of human papillomaviruses (HPV), most frequently HPV16, are causally associated with a subset of head and neck squamous cell carcinomas (HNSCC). HPV DNA associated tumors appear to be heterogeneous in prevalence over time and geographically, in the oncogenic activity (direct and indirect viral markers) and clinical behavior. However, it remains unclear which biomarkers can reliably determine which HNSCC are truly driven by HPV transformation.
Aims: In the present thesis, the first aim was to determine the prevalence of the truly HPV-associated HNSCC tumors in North-East Italy. The second aim, was to investigate the association of HPV DNA positivity with other viral (viral load, oncoE6 protein, HPV antibodies) and cellular (p16INK4a, pRb) markers. The third aim, was to evaluate the prognostic significance of HPV-association tumors for clinical outcome (i.e. survival).
Materials and Methods: Overall, 247 fresh frozen and 53 (21%) formalin-fixed paraffin-embedded (FFPE) tumor tissue biopsies and 102 (41%) sera were collected from 247 newly detected HNSCC patients from North-East Italy. Clinical parameters for each patient were obtained from the clinical database.
HPV DNA was determined by polymerase chain reaction (PCR) with consensus MY09/MY11 primers and Restriction Fragment Length Polymorphism (RFLP) analysis and/or BSGP5+/6+-PCR/Multiplex Papillomavirus Genotyping (MPG) capable of detecting all known 51 mucosal HPV types.
The HPV DNA+ tumor tissues were further analyzed for i) viral load by HPV16 qPCR and quantitative BSGP5+/6+-PCR/MS; ii) detection of HPV E6*I transcripts by RT-PCR; iii) expression levels of cellular protein p16INK4a and pRb by IHC; and iv) presence of HPVE6 protein for types 16 and 18 by the commercial OncoE6TM Oral Test; Antibodies to HPV early and late proteins of the eight most frequent high-risk HPV types were determine din all available sera by bead-based multiplex serology.
Results: Overall, HPV DNA+ was 8.5% (21/247), type 16 was detected in 95% (20 cases) and type 58 in 5% (1 case). No multiple infections were detected. The HPV RNA+ was 6% (14/244). Oropharynx was the site with the highest HPV prevalence by DNA (27%) and RNA (20%). In the other anatomic sites, HPV prevalence was < 8%.
Among the HPVDNA+ RNA+ tumors, i) 93% of the HPV16+ tissues (13/14) showed high viral load; ii) 60% (6/10) showed both up-regulation of p16INK4a and down-regulation of pRb; iii) and in 100% (8/8) HPV16 E6 oncoprotein was detected. All sera of 7 HPV-driven tumors showed strong positive antibody reactions with HPVE6 and E7 proteins, 6 for type 16 and 1 for type 58, type-concordant with the related tumor. Another single serum HPV16 DNA+ in the tumor, showed positivity for all early HPV16 proteins suggestive of an HPV-driven tumor. Kaplan-Meier analyses for the oropharynx showed a trend for better survival in the HPV-associated group than in the HPV negative ones.
Conclusions: A low HPV prevalence was found in HNSCC of the population living in the North-East of Italy. Oropharynx was the preferential site for HPV infection while the HPV prevalence in the other anatomic sites appeared negligeable. We observed that the HPVDNA+ RNA+ samples showed a good correlation with the other markers like high viral load, presence of the E6 oncoprotein, and HPVE6 and E7 seromarkers. In contrast to recent reports we did not find a good correlation between HPVDNA+ RNA+ and the up-regulation of p16INK4a and down-regulation of pRb. Survival analyses showed a better prognosis in the HPV-driven patients with tumors occurring in the oropharynx.<br>Il papillomavirus umano (HPV), più frequentemente il tipo 16, sono causalmente associati agli tumori squamosi di testa collo (HNSCC). Questi tumori sono caratterizzati da un'elevata eterogeneità geografica e una migliore risposta alla terapia.
L'obiettivo di questo studio è di valutare la prevalenza e l'attività biologica di HPV in HNSCC nel nord dell'Italia. La genotipizzazione per se non è sufficiente a definire il ruolo del virus nella patogenesi HNSCC. E' necessario analizzare e verificare la presenza di altri marker diretti come i trascritti virali, la carica virale, oncoE6 proteine e anticorpi HPV e dei marker indiretti come l'espressione delle proteine cellulari p16INK4a e pRb. I risultati ottenuti sono stati alla fine correlati con la sopravivenza.
Nel presente studio sono stati arruolati 247 pazienti del Nord-Est dell'Italia. Sono stati raccolti biopsie tumorale congelate per tutti i pazienti, e per un sottogruppo dei blocchetti di paraffina e del plasma.
La presenza del DNA virale è stato determinato con i) reazione a catena della polimerasi con primer consenso MY09/MY11 e tipizzazione con digestione enzimatica e/o ii) BSGP5+/6+ -PCR/Multiplex Papillomavirus Genotype (MPG). I casi HPV DNA positivi sono stati ulteriormente analizzati per: i) carica virale (quantitative PCR); ii) presenza dei trascritti virali (E6*I method); iii) l'espressione delle proteine cellulari p16INK4a e pRb (immunohistochimica, IHC); iv) espressione dell'oncoproteina E6 (OncoE6TM kit, AVC); v) anticorpi anti HPV (Multiplex HPV serology).
La prevalenza basata sulla positività del DNA virale era del 9% (21/247). HPV16 è stato trovato nel 95% (20/21) dei casi, 1 HPV58 è stato identificato come infezione singola. La prevalenza basato sul HPV DNA+RNA+ era del 6% (14/244). L'orofaringe era il sito con la più elevata prevalenza di HPV (HPV DNA+ = 27%, HPV DNA+ RNA+ = 20%). 86% (12/14) dei campioni aveva un'alta carica virale per il tipo analizzato; ii) over espressione p16INK4a nel 90% (9/10), down-regulation pRb nel 55% (6/11); iii) la presenza dell'oncoproteina E6 era presente nel 100% (8/8) dei casi testati. La presenza di anticorpi anti HPV è stata valutata in 102 plasmi; 8 su 102 erano positivi per anticorpi HPV, con elevata correlazione con lo status HPV dei relativi tessuto tumorale. Le analisi di Kaplan-Meier per l'orofaringe hanno mostrato un trend di migliore sopravvivenza nei pazienti con tumori HPV positivi per DNA e RNA rispetto ai pazienti HPV negativi.
Bassa prevalenza di HPV nei tumori testa collo nel nord dell'Italia confrontato ad altri paesi. L'orofaringe rimane il sito prediletto dell'infezione per l'HPV (27 %). HPV16 era il principale tipo trovato (95%). Migliore sopravvivenza dei pazienti con tumori HPV positivi.
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Paccione, Rachel J. "Vimentin Overexpression Contributes To the Biological Properties of Metastatic Head and Neck Cancer Cells." VCU Scholars Compass, 2005. http://scholarscompass.vcu.edu/etd/1084.
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Epithelial to mesenchymal transition occurs in the later stages of epithelial tumor progression, with cells expressing mesenchymal markers. Of these, the intermediate filament protein vimentin is frequently upregulated in metastatic carcinomas. Previously, microarray studies showed that the gene encoding vimentin is highly upregulated in metastatic HN12 cells compared to a related primary tumor cell line. In this study, we confirmed this difference using real-time quantitative PCR, western blot analysis, and immunostaining. Furthermore, EGF and TGF-β, growth factors that induce migration and invasion of HN12 cells, produced synergistic increases in vimentin expression. To assess the contribution of vimentin to the biological properties, HN12 cells were stably transfected with a plasmid that directs synthesis of vimentin shRNA. Clones expressing decreased amounts of vimentin were isolated and characterized. These cells showed significantly reduced proliferation compared to non-targeting controls. Moreover, downregulation of vimentin led to a decrease in cell motility, as well as reducing their ability to invade through a basement membrane substitute. Using transient transfection assays, vimentin promoter activity was determined in HN12 cells to define regulatory elements important for controlling vimentin upregulation in the absence or presence of EGF and TGF-β. Taken together, the data indicate that overexpression of vimentin is important for proliferation and invasion of metastatic HN12 cells, and suggest that EGF- dependent pathways target binding elements in the proximal vimentin promoter, while TGF-β is likely to act in an AP1-dependent manner. Furthermore, both growth factors appear to synergize by stimulating promoter activation through the ASE site, suggesting involvement of Stat-dependent pathways in regulation of vimentin expression in HN12 cells.
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Hoffmann, Caroline. "Dendritic Cells in Head and Neck Cancer Microenvironment : From Mechanisms to Biomarkers." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS308/document.
Texte intégralRésumé :
L’objectif de ce travail était de comprendre l’état moléculaire des cellules dendritiques (CD) dans le microenvironnement tumoral. En intégrant l’analyse de tumeurs humaines par cytométrie en flux, de transcriptome, de secretome tumoral et l’analyse d’une base de données d’interaction CD-lymphocyte T générées in vitro, j’ai obtenus 2 résultats majeurs. Tout d’abord, nous proposons une nouvelle classification de CD activées humaines, qui sont soit « secrétantes », c’est-à-dire spécialisées dans la production de cytokines et chemokines, soit « aidantes » c’est-à-dire spécialisées dans l’induction de la sécrétion de nombreuses cytokines T helper après co-culture. Les CD infiltrant les tumeurs ORL inflammées correspondaient au type « sécrétantes ». Au-delà du nouveau concept biologique, cette classification est base théorique importante pour l’immunothérapie à base d’adjuvants. Deuxièmement, nous avons montré que l’inflammation tumorale n’était pas un facteur pronostic majeur des cancers ORL, mais que MMP2 et l’effraction extra-capsulaire étaient des facteurs pronostiques indépendants de la survie liée à la maladie. Nous avons pu classer les patients en 4 niveaux de risque et montré qu’ils avaient des chances équivalentes de réponse à l’immunothérapie. Nos données sont une base pour un essai clinique dirigé par biomarqueur, proposant de la chimiothérapie ou de l’immunothérapie néoadjuvantes, dans le but de diminuer le pourcentage de patients présentant des récidives sévères et précoces<br>The objective of the thesis was to decipher the molecular state of tumor infiltrating dendritic cell (DC) and their relation to the tumor microenvironment. By combining the analysis of human tumor samples by flow cytometry and RNA sequencing, of tumor secretome and of a large dataset of in vitro DC-Tcell interactions I obtained 2 main findings. First, we reported a novel classification of human activated DC, that are either “secretory” that is specialized in secreting cytokines and chemokines, or “helper” that is specialized at inducing the secretion of a broad range of T helper cytokines after cell co-culture. DC infiltrating inflamed human head and neck cancer matched the “secretory” phenotypic and transcriptomic signatures. Beyond this novel biological concept, this classification is of importance as a theoretical basis for adjuvant-based immunotherapy. Secondly, we showed that tumor inflammation was not the main prognostic factor for oral cavity cancer (OCC) patients, but that MMP2 and the presence of extra-nodal extension were independent predictors of reduced disease-specific survival. We could stratify OCC into 4 prognostic groups and showed that they had similar expected rates of response to immunotherapy. Our data may serve to design a biomarker-driven clinical trial proposing neoadjuvant chemotherapy or immunotherapy to high-risk patients, with the goal of reducing the percentage of OCC patients that will present with early and severe recurrences
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Berthon, Beatrice. "Optimisation of Positron Emission Tomography based target volume delineation in head and neck radiotherapy." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/69184/.
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Automatic segmentation of tumours using Positron Emission Tomography (PET) was recommended for radiotherapy treatment (RT) planning of head and neck (H&N) cancer patients, and investigated in the scientific literature without reaching a consensus on the optimal process. This project aimed at evaluating the performance of PETCbased automatic segmentation (PETCAS) methods and developing an optimal PETC AS process to be used at Velindre Cancer Centre (VCC). For this purpose, ten algorithms were implemented to represent the most promising PETCAS approaches from a systematic review of the literature. The algorithms’ performance was evaluated on filled phantom inserts with variable size, geometry, tumour intensity and image noise. The impact of thick insert plastic walls on both image quantification and segmentation was thoroughly assessed. The PETCAS methods were further applied to realistic H&N tumours, modelled using a printed subresolution sandwich phantom developed and calibrated in house. Results showed that different PETCAS performed best for different types of target objects. An Advanced decision TreeCbased Learning Algorithm for Automatic Segmentation (ATLAAS) was therefore developed and validated for the selection of the optimal PETCAS approach according to the target object characteristics. Finally, a protocol was designed for the use of PETCAS within RT planning at VCC. The protocol was used retrospectively on a group of 10 oropharyngeal cancer patients, and the results highlighted the additional information brought by PET beyond anatomical imaging. In a prospective study on 10 additional patients, PETCAS replaced manual PET/CT delineation, and accounted for up to 33% of the modifications of manually drawn CT/MRI contours to derive the final planning contour. This study demonstrated the usefulness and reliability of the PETCAS method in RT planning, and led to modifying the clinical workflow for H&N patients at VCC. This work has the potential to be extended to other tumour sites and institutions.
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Cupparo, Ilaria. "Region growing and fuzzy C-means algorithm segmentation for PET images of head-neck tumours." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2019. http://amslaurea.unibo.it/18020/.
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The aim of this work, performed at Azienda Ospedialiero Universitaria in Modena, is the implementation and validation of autosegmentation methods of head and neck (H&N) tumor PET images. These autosegmentation processes are important mostly to overcome the problems of manual segmentation, performed by radiotherapist physician, regarding the contouring time (that can reach more than two hours) and the intra-observer and inter-observer variability. Fuzzy C-means (FCM) and Region Growing (RG) algorithms were developed in a MATLAB GUI that allows to choice iteratively the different steps necessary for a good segmentation. Pre-processing operations were previously applied to improve image quality: a gaussian filter to remove noise and an opening morphological operation to uniform background. NEMA IEC body phantom, acquired with four hot spheres and two cold spheres, was firstly used to test the two methods in known condition. The accuracy of processes was evaluated considering the volume change between calculated and theoretical volume that is always null within error and reaches the highest value in the case of the smallest sphere because of partial volume effect, generally decreasing as sphere size increases. Afterwards, 16 PET images studies of H&N tumors were used for clinical test of algorithms. The efficiency was estimated using two quantitative coefficients: Dice Similarity Index (DSC) and Average Hausdorff Distance (AHD). Mean DSC and AHD values, obtained mediating on all cases, are within literature threshold (0.6 for DSC and about 16 mm for AHD). Contouring time, required to segment all slices of each case, changes from few seconds in FCM to some minutes in RG, always remaining inferior to manual segmentation time. The results are satisfactory, however, they could be improved increasing the number of patients and testing the variability between more experts. FCM could be also applied to lymphomas to test the efficiency in the segmentation of displaced regions.
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Hakelius, Malin. "Interactions between Malignant Keratinocytes and Fibroblasts : Studies in Head and Neck Squamous Cell Carcinoma." Doctoral thesis, Uppsala universitet, Plastikkirurgi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-221109.
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Carcinoma growth requires a supportive tumor stroma. The concept of reciprocal interactions between tumor and stromal cells has become widely acknowledged and the connective tissue activation seen in the malignant process has been likened to that of a healing wound. Little is, however, known about the specific characteristics of these interactions, distinguishing them from the interplay occurring between epithelial and stromal cells in wound healing. In order to study differences in the humoral effects of malignant and benign epithelial cells on fibroblasts, we used an in vitro coculture model with human oral squamous cell carcinoma cells (SCC) or normal oral keratinocytes (NOK) on one side of a semi-permeable membrane and fibroblasts seeded in gels on the other. Pro-collagens α1(I) and α1(III) were more downregulated in NOK cocultures compared to SCC cocultures. IL-1α was identified as a major keratinocyte-derived soluble factor behind the effects observed. We concluded that SCC are less antifibrotic compared to NOK. There was also a differential expression among enzymes involved in ECM turnover. The urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) were both upregulated by NOK, but not by SCC. Here, rIL-1ra caused further upregulation of PAI-1. Global gene expression in fibroblasts was assessed using Affymetrix™ arrays. In total, 82 transcripts were considered differentially expressed; 52 were up- and 30 were downregulated in SCC compared to NOK cocultures. Among the differentially expressed genes there was an enrichment of genes related to collagens and to a nonspecific, innate-type response. The innate response marker pentraxin (PTX3) was upregulated by keratinocyte-derrived IL-1α in both NOK and SCC cocultures. We observed a considerably higher IL-1α / IL-1ra quotient in SCC cocultures, however, while PTX3 mRNA upregulation was higher in SCC cocultures, there was no difference in the level of PTX3 secreted protein. Taken together, we concluded that NOK and SCC regulate genes important for ECM composition and for the innate immune-response differentially. IL-1α was identified as one important mediator of the observed effects. In general, SCC appeared to be more profibrotic in their effects on fibroblasts.
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Dahlgren, Liselotte. "Studies on the presence and influence of human papillomavirus (HPV) in head and neck tumors /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-289-6/.
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Ansell, Anna. "Identification of Tumor Cell- and Stroma Derived Biomarkers of Treatment Response in Head and Neck Cancer." Doctoral thesis, Linköpings universitet, Avdelningen för neurovetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-100734.
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Head and neck squamous cell carcinoma (HNSCC) poses a major health problem in the world with approximately 600 000 new cases yearly. Treatment resistance is a major problem within this patient group and despite advances in treatment strategies the overall survival rate has unfortunately not increased. One of the major components of the tumor microenvironment is the cancer associated fibroblasts (CAFs) which can modulate the treatment sensitivity, tumor growth, and the invasive potential of tumor cells. The aim of this thesis was to identify predictive markers for treatment response in HNSCC and to study the crosstalk between tumor cells and CAFs that may underlie treatment resistance. In paper I, we identified gene expression differences between one cisplatin sensitive cell line and two cisplatin resistant cell lines, by microarray analysis, and found that a high expression of matrix metalloproteinase (MMP) -7 was associated with resistance to cisplatin. In paper II, the epidermal growth factor (EGF) receptor ligands EGF, amphiregulin, and epiregulin were evaluated regarding their potential use as predictive biomarkers for cetuximab treatment response in tongue cancer cell lines and it was shown that EGF may serve as a marker for poor cetuximab response. In paper III and IV, we investigated the influence of CAFs on the proliferation, migration, gene expression, and cetuximab response of tumor cells. It was found that CAFs induced resistance to cetuximab in a MMP-dependent manner. In addition, a microarray analysis, comparing tumor cells co-cultured with CAFs and tumor cells cultured alone, revealed that CAFs induced multiple gene expression changes in tumor cells some of which are related to epithelial to mesenchymal transition. Some of these changes were found to be dependent on cell-cell contact. Taken together, we here suggest MMP-7 and EGF to be predictive markers of cisplatin and cetuximab response, respectively. We also show that CAFs protect HNSCC cells from cetuximab treatment; however, the factor responsible for the protective effect is yet to be discovered.
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Macedo, Gonzales Rodney. "Development of therapeutic vaccine strategies and pre-clinical animal tumor models for head and neck cancers." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066269/document.
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Les cancers des voies aéro-digestives supérieures, liés à la consommation d'alcool et de tabac mais également à l'HPV-16, ont un pronostic médiocre malgré les traitements actuels. Le développement de nouvelles stratégies innovantes dans des modèles précliniques adaptés est ainsi nécessaire. Nous avons préalablement développé une stratégie vaccinale ADN permettant l'auto-assemblage in vivo de pseudo-particules virales non infectieuses exprimant l'oncoprotéine E7 de l'HPV-16 (pVLP-E7). Nous avons notamment montré que l'injection de pVLP-E7 en intradermique (ID) était capable d'induire de bonnes réponses anti-tumorales dans un modèle murin de cancer obtenu en injectant dans le flanc des cellules d'une lignée exprimant les antigènes E6 et E7 de l'HPV-16, mais qu'il était nécessaire d'ajouter des adjuvants de types agoniste de TLR 7 et 9 dans des tumeurs avancées. Afin de tester de nouvelles voies vaccinales dans un modèle pertinent, nous avons développé un modèle orthotopique intrabuccal présentant des caractéristiques anatomiques et inflammatoires plus proches des cancers observés chez l'homme que le modèle ectopique. Dans ce modèle, nous avons testé une voie vaccinale muqueuse intrajugale qui a montré de meilleures réponses T CD8+ spécifiques en comparaison à la voie ID. Nous avons montré que ce type de vaccination en association à des adjuvants, était efficace dans des tumeurs établies, en lien avec une infiltration intratumorale et ganglionnaire de lymphocytes T CD8+ spécifique, permettant également une protection lors de rechallenge tumoral. Cette stratégie apparaît donc prometteuse dans le traitement de ces cancers fréquemment récidivants<br>Head and neck squamous cell cancer (HNSCC) associated with alcohol and tobacco consumption, and recently with human papillomavirus-16 (HPV-16), have bad prognosis despite current therapies. Development of innovative vaccine strategies and adequate pre-clinical tumor models are required to better evaluate HNSCCs. We developed a DNA vaccination that creates non-infectious virus-like particles, which express HPV-16 E7 oncoprotein (pVLP-E7). Results showed that pVLP-E7 induced an E7-specific immune response in vivo and in vitro. Moreover, using an ectopic model of HNSCC that expresses E6/E7 (TC-1), we found that pVLP-E7 intradermic (ID) immunizations induced anti-tumoral responses at early stages. For larger established tumors, pVLP-E7 vaccines were only efficient when administered with TLR-7 and TLR-9 agonists. In an orthotopic model that shares anatomical and inflammatory features with human HNSCC we observed that intra-cheek (IC) infusion of either TC-1 or NR-S1 cells into mice elicited higher numbers of inflammatory infiltrates in the tumor compared to ectopic models. Using this orthotopic IC model, we found that mucosal IC pVLP-E7 vaccination elicited better vaccine-specific CD8+ T-cell responses than ID administration in naive and tumor-bearing mice. Furthermore, pVLP-E7 IC immunizations in combination with TLR agonists led to rejection of established tumors and long-term protection, both of which were associated with E7-specific CD8+ T cell infiltration in tumors and lymph nodes. Our findings demonstrate that pVLP-E7 IC vaccination with adjuvants is efficient against these tumor models and together provides a valuable therapeutic strategy for HNSCCs
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Gillgren, Peter. "Body site of cutaneous malignant melanoma : primary tumor location in relation to phenotypic and prognostic factors /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-339-2.
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Aslam, Mohammed Afeef. "An investigation of GRP78 expression and inhibition in squamous cell carcinoma of the head and neck." Thesis, University of Liverpool, 2011. http://livrepository.liverpool.ac.uk/3813/.
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GRP78 is a known cyto-protective gene which is induced in microenvironments typical of tumours with low glucose and hypoxia. Furthermore up-regulation of GRP78 has been linked to chemo- and radioresistance as well as poor survival outcome. This study is the first to confirm that GRP78 is up-regulated in tumours of the oropharynx, larynx and hypopharynx compared with matched histologically normal tissue (p(Χ2)<0.001). Up-regulation of GRP78 may be important for tumour development and therefore we have investigated the consequences of inhibition of GRP78 in cells derived from laryngeal squamous cell carcinomas (LSCC). EGF-SubA is a novel drug consisting of EGF covalently attached to the A subunit of an E.coli derived AB5 toxin which can cleave GRP78. EGF-SubA was able to induce EGFR-dependent cytotoxicity in a panel of seven laryngeal SCC cells with an IC50 range of between 4-100pM. EGF-SubA treatment induced G1 cell cycle arrest as well as apoptosis. Therefore apoptosis may be the mechanism by which EGF-SubA causes cell death. In vitro studies demonstrated that EGF-SubA enhances the effects of clinically relevant genotoxic agents. Two Gy survival fractions (SF2) were significantly reduced with EGF-SubA pre-treatment (p<0.03). In addition EGF-SubA in combination with the primary head and neck cancer chemo-therapeutic agent cisplatin, resulted in IC50 drug combination indexes (CI) as low as 0.542, which is suggestive of a synergistic effect. The potency of EGF-SubA appears to be substantially dependent on EGFR membrane expression since cells expressing higher EGFR levels were associated with increased sensitivity to EGF-SubA where Spearman’s rank correlation coefficient = 0.919 (p=0.003). Furthermore pre-incubation of LSCC cells with sub-toxic doses of cetuximab, a therapeutic monoclonal antibody to EGFR, completely rescued cells from the cytotoxic effects of EGF-SubA (p(t test)≤0.005). This is an important proof of principal for a proposed combined toxin-protectant therapeutic strategy that would permit topical use of EGF-SubA peri- or post-operatively after tumour resection in order to kill any remaining tumour cells, or as an oral rinse in patients who present with pre-malignant lesions of the oral cavity, with any potential systemic toxicity being abrogated by cetuximab. In summary this study has found that GRP78 is up-regulated in head and neck cancers suggesting that this protein may be important for tumour development and survival. Thus inhibition of GRP78 through EGF-SubA may offer a novel approach to cancer therapy. In addition to suppressing the growth of LSCC cell, EGF-SubA was found to enhance the effects of relevant genotoxic agents in vitro of cisplatin and radiation. Further work is now warranted in order to assess the efficacy and toxicity of EGF-SubA, in vivo, before phase I clinical trials can commence.
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Cederblad, Lena. "Aspects on Head and neck Cancer with special reference to Salivary Gland Tumours and Single Nucleotide Polymorphism." Doctoral thesis, Uppsala universitet, Institutionen för immunologi, genetik och patologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-332192.
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A thesis on Head and neck cancer focusing on dose planning, salivary gland carcinoma and Single nucleotide polymorphism. For dose planning PET/CT (Positron emissions tomography/computed tomography) with tracer gave more precise information in comparison dose planning with CT. More primary tumours and metastases were found with the acetate tracer than with glucose tracer. Acetate PET/CT also showed larger volume of tumours attributed to lipid metabolism. In a retrospective study salivary gland cancer 5-year overall survival (OS) was 53 %. Salivary gland carcinoma consists of many histopathological groups, the two largest groups being mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ASCC). For ACC, having the best 5-year OS, it was 70 percent. Facial palsy, advanced stage disease, lymph node metastases worsened prognosis. ACC and polymorphous low grade carcinoma (PLGA) expressed c-myc and cyclin D1 to a larger extent than MEC. In squamous cell carcinoma of the head and neck we examined the occurrence of Single Nucleotide polymorphism, SNP. We found that the SNPs in male and female patients differed from each other. In male patients the SNPs were associated with immune response while in female patients the association was to SNPs concerning inflammation. This means that different pathways were engaged in cancer development for men and women. We also found that the SNPs in patients were different from those expressed in the healthy controls.
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Dounis, Evangelia. "Effect of irradiation of head and neck tumours on the proteins' composition of the enamel salivary pellicle." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11163744.
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Dong, Lixin. "DIFFUSE OPTICAL MEASUREMENTS OF HEAD AND NECK TUMOR HEMODYNAMICS FOR EARLY PREDICTION OF CHEMO-RADIATION THERAPY OUTCOMES." UKnowledge, 2015. http://uknowledge.uky.edu/cbme_etds/35.
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Chemo-radiation therapy is a principal modality for the treatment of head and neck cancers, and its efficacy depends on the interaction of tumor oxygen with free radicals. In this study, we adopted a novel hybrid diffuse optical instrument combining a commercial frequency-domain tissue oximeter (Imagent) and a custom-made diffuse correlation spectroscopy (DCS) flowmeter, which allowed for simultaneous measurements of tumor blood flow and blood oxygenation. Using this hybrid instrument we continually measured tumor hemodynamic responses to chemo-radiation therapy over the treatment period of 7 weeks. We also explored monitoring dynamic tumor hemodynamic changes during radiation delivery. Blood flow data analysis was improved by simultaneously extracting multiple parameters from one single autocorrelation function curve measured by DCS. Patients were classified into two groups based on clinical outcomes: a complete response (CR) group and an incomplete response (IR) group with remote metastasis and/or local recurrence within one year. Interestingly, we found human papilloma virus (HPV-16) status largely affected tumor homodynamic responses to therapy. Significant differences in tumor blood flow index (BFI) and reduced scattering coefficient (μs’) between the IR and CR groups were observed in HPV-16 negative patients at Week 3. Significant differences in oxygenated hemoglobin concentration ([HbO2]) and blood oxygen saturation (StO2) between the two groups were found in HPV-16 positive patients at Week 1 and Week 3, respectively. Receiver operating characteristic curves were constructed and results indicated high sensitivities and specificities of these hemodynamic parameters for early (within the first three weeks of the treatment) prediction of one-year treatment outcomes. Measurement of tumor hemodynamics may serve as a predictive tool allowing treatment selection based on biologic tumor characteristics. Ultimately, reduction of side effects in patients not benefiting from radiation treatment may be feasible.
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Maxim, Nicolas T. Mr. "Tumor-Specific Cell Death Induction by Noxa Overexpression for Head and Neck Squamous Cell Carcinoma (HNSCC) Treatment." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4230.
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The primary focus of this research is the mechanisms of cell death in head and neck squamous cell carcinoma (HNSCC) treatment. These cancers typically originate in squamous cells that line the moist mucosal surfaces of head and neck. HNSCC is commonly treated with a platinum based agent, cisplatin. While the drug does offer strong antitumor effects, its prolonged use often results in tumor-acquired resistance, which limits treatment effectiveness. We have shown that cisplatin treatment induces the expression of a pro-apoptotic BCL-2 family member Noxa, which then initiates caspase- dependent apoptosis through its binding and sequestration of pro-survival protein MCL-1 for its inactivation. Without Noxa induction, cell death is significantly reduced when treating HNSCCs with cisplatin. The objectives of this study are (1) to determine the molecular mechanisms by which Noxa induces cell death in HNSCC cells; (2) to determine the molecular mechanisms of cisplatin-resistance in isogenic HNSCC cell lines.
We observed an increase of apoptosis by ectopic expression of Noxa in all HNSCC cell lines tested, but not in immortalized human normal oral keratinocytes (NOK), suggesting that Noxa overexpression is sufficient to induce tumor-specific cell death. Noxa-induced cell death was mediated by BAX and BAK activation. BAK activation was mediated through Noxa binding to MCL-1, but not BCL-XL. Cisplatin- resistant cells induced less Noxa and apoptosis, supporting that Noxa induction is prerequisite for apoptosis induced by cisplatin. Taken together, Noxa induces tumor- specific cell death in HNSCC cells primarily through BAX and BAK activation, which suggests the therapeutic potential of this protein.
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CHITI, LAVINIA ELENA. "GAMMA-PROBE GUIDED SENTINEL LYMPH NODE EXTIRPATION TO ASSESS PATTERNS OF NODAL METASTASIS IN SPONTANEOUS HEAD AND NECK MALIGNANCIES OF THE DOG: A SECOND STEP BASED ON PREVIOUS EXPERIENCES ON MAST-CELL TUMORS." Doctoral thesis, Università degli Studi di Milano, 2022. http://hdl.handle.net/2434/916665.
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Canine oncology has recently reported interest in the detection of occult nodal metastases, and efforts have been made to identify the best strategy for accurate nodal staging. In this scenario, the present PhD thesis was aimed to improve knowledge on the current understanding of the feasibility and impact of sentinel lymph node (SLN) mapping with radiopharmaceutical and blue dye in cancer-bearing dogs. Initially, we evaluated the technique in canine mast cell tumors (MCT), given the high prevalence of this tumor type, the propensity for lymphatic spread and recognized prognostic impact of nodal metastases. Thirty client-owned dogs with 34 MCT were included. At least one SLN was identified in all but 3 dogs that had a scar from previously excised MCT, and in 30 cases (63%) the SLN did not correspond to the regional lymph node (RLN). As a second step, we explored the impact of SLN mapping and extirpation in dogs with head and neck tumors, given the well-accepted unpredictability of patterns of nodal metastases. Twenty-three dogs with tumors of the head and neck and absence of clinically evident nodal disease (cN0 neck) were prospectively included and underwent tumor excision and SLN extirpation. Reported detection rate was 83%, with at least one SLN identified in all but 4 dogs with thyroid tumors. In 52% of dogs, the SLN did not correspond to the RLN and at histopathology 42% of dogs had nodal metastases, of which 4 differed from the RLN. As the last step of this PhD project, we conducted an explorative study to identify clinical or pathological characteristics that could allow for identification of dogs with MCT at lower risk of SLN metastases, that could be excluded a priori from the SLN mapping and extirpation. Surprisingly, tumor grade was not able to predict the risk of having HN2-3 or HN3 SLN and the only variables that correlated with nodal metastases were tumor size, number or SLN and subcutaneous MCT. Given low to moderate discriminant ability, however, none of these variables could safely determine the exclusion of patients from the procedure.
Results of the present project underscore the utility of implementation of SLN biopsy in the management of dogs with MCT and head and neck tumors, given the low correspondence between clinically expected RLN and SLN and the high rate of occult nodal metastases that could be detected with this procedure. Future research should be aimed at investigating the impact on long-term prognosis and disease free interval of the extirpation of metastatic SLN, and identify variables that could allow for exclusion of low-risk patients from the procedure.
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Hristozova, Tsvetana [Verfasser]. "Characterization of circulating tumor cells in locally advanced squamous cell carcinoma of the head and neck / Tsvetana Hristozova." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2012. http://d-nb.info/1030380716/34.
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