Thèses sur le sujet « Small Cell Lung Cancer »
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Sarvi, Sana. « Small cell lung cancer and cancer stem cell-like cells ». Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9542.
Texte intégralKapeleris, Joanna C. « Circulating tumour cells in non-small cell lung cancer ». Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228607/1/Joanna_Kapeleris_Thesis.pdf.
Texte intégralWang, Wei. « Modulation of immune cell responses by small cell lung cancer cells ». Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/modulation-of-immune-cell-responses-by-small-cell-lung-cancer-cells(7bdc85c2-acd8-4f13-9d2b-e2ce07d1567b).html.
Texte intégralOosterhout, Anselmus Gerardus Maria van. « Small cell lung cancer and brain metastasis ». Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1995. http://arno.unimaas.nl/show.cgi?fid=6643.
Texte intégralSeute, Tatjana. « Neurologic complications in small cell lung cancer ». Maastricht : Maastricht : Universiteit Maastricht ; University Library, Universiteit Maastricht [host], 2008. http://arno.unimaas.nl/show.cgi?fid=9520.
Texte intégralMacaulay, Valentine. « Growth regulation in small cell lung cancer ». Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47547.
Texte intégralSikkink, Stephen K. « Genetic pathology of non-small cell lung cancer ». Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250405.
Texte intégralBrena, Romulo Martin. « Aberrant DNA methylation in human non-small cell lung cancer ». Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1172083621.
Texte intégralWong, Wing-sze, et 黃詠詩. « Fusion genes in non-small cell lung cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43781378.
Texte intégralNg, Sheng Rong. « CRISPR-mediated interrogation of small cell lung cancer ». Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/117782.
Texte intégralThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged student-submitted from PDF version of thesis. Vita.
Includes bibliographical references.
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung carcinoma that remains among the most lethal of solid tumor malignancies. Despite decades of research, treatment outcomes for SCLC remain very poor, highlighting the need for novel approaches to target the disease. Recent genomic sequencing studies have identified multiple recurrently altered genes in human SCLC tumors, many of which remain to be functionally validated. Genetically engineered mouse models (GEMMs) of SCLC have been developed that recapitulate many key features of human SCLC. These models have been used extensively to investigate various aspects of SCLC biology, including tumor initiation, progression and metastasis. The development of the CRISPR-Cas9 system has greatly facilitated genome editing in mammalian cells, leading to its widespread adoption for various applications in cancer biology. We have utilized this system in two complementary ways to investigate the molecular mechanisms involved in SCLC initiation, progression and maintenance. Firstly, we have adapted the CRISPR-Cas9 system for use in GEMMs of SCLC, to enable rapid modeling and functional validation of candidate tumor suppressor genes in vivo. Using this system, we have demonstrated that p107, a member of the retinoblastoma family that is mutated in a significant fraction of human SCLC tumors, is a functional tumor suppressor in SCLC. Notably, loss of p107 in SCLC tumors resulted in significant phenotypic differences compared with loss of its close relative, p130. We also demonstrated that CRISPR-induced mutations can be used to infer lineage relationships between primary and metastatic tumors in the same animal. Secondly, we have performed a CRISPR-based genetic screen, utilizing a custom sgRNA library targeting the druggable genome, to identify novel SCLC-specific genetic vulnerabilities. We found that SCLC cells displayed enhanced sensitivity towards disruption of several key metabolic pathways, including the de novo pyrimidine biosynthesis pathway. Pharmacological inhibition of Dhodh, a key enzyme in this pathway, reduced the viability of SCLC cells in vitro and strongly suppressed SCLC tumor growth in vivo, validating this pathway as a promising therapeutic target in SCLC. Taken together, the work presented here demonstrates the utility of the CRISPR-Cas9 system for performing functional interrogation of SCLC.
by Sheng Rong Ng.
Ph. D.
Lawson, Malcolm Hedley. « Determinants of chemoresistance in small cell lung cancer ». Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609102.
Texte intégralHodkinson, Philip Simon. « Tumour microenvironment interactions of small cell lung cancer ». Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4254.
Texte intégralSwinson, Daniel. « Hypoxic markers in non-small cell lung cancer ». Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/29476.
Texte intégralMoka, Nagaishwarya, Manisha Nukavarapu, Jennifer Phemister et Mckinney Jason. « Small cell lung cancer(SCLC) disguised as Dysphagia ». Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/168.
Texte intégralWong, Wing-sze. « Fusion genes in non-small cell lung cancer ». Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43781378.
Texte intégralWong, Kit-man Sunny, et 王傑民. « Isolation and characterization of cancer stem cells in non-small cell lung cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47250665.
Texte intégralpublished_or_final_version
Pathology
Master
Master of Philosophy
Brattström, Daniel. « Angiogenesis related markers in non-small cell lung cancer / ». Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl.[distributör], 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3558.
Texte intégral陳潔盈 et Kit-ying Loucia Chan. « Expression analysis of Candidate cancer genes in non-small cell lung cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45011163.
Texte intégralStordal, Britta Kristina. « Regrowth resistance in platinum-drug resistant small cell lung cancer cells ». Bill Walsh Cancer Research Laboratories, Royal North Shore Hospital and The University of Sydney, 2007. http://hdl.handle.net/2123/2467.
Texte intégralThe H69CIS200 cisplatin-resistant and H69OX400 oxaliplatin-resistant cell lines developed as part of this study, are novel models of low-level platinum resistance. These resistant cell lines do not have common mechanisms of platinum resistance such as increased expression of glutathione or decreased platinum accumulation. Rather, these cell lines have alterations in their cell cycle allowing them to proliferate rapidly post drug treatment in a process known as ‘regrowth resistance’. This alteration in cell cycle control has come at the expense of DNA repair capacity. The resistant cell lines show a decrease in nucleotide excision repair and homologous recombination repair, the reverse of what is normally associated with platinum resistance. The alterations in these DNA repair pathways help signal the G1/S checkpoint to allow the cell cycle to progress despite the presence of DNA damage. The decrease in DNA repair capacity has also contributed to the development of chromosomal alterations in the resistant cell lines. Similarities in chromosomal change between the two platinum resistant cell lines have been attributed to inherent vulnerabilities in the parental H69 cells rather than part of the mechanism of resistance. The H69CIS200 and H69OX400 resistant cells are cross-resistant to both cisplatin and oxaliplatin. This demonstrates that oxaliplatin does not have increased activity in low-level cisplatin-resistant cancer. Oxaliplatin resistance also developed more rapidly than cisplatin resistance suggesting that oxaliplatin may be less effective than cisplatin in the treatment of SCLC. The resistant cell lines have also become hypersensitive to taxol but show no alterations in the expression, polymerisation or morphology of tubulin. Rather, the PI3K/Akt/mTOR pathway is involved in both platinum resistance and taxol sensitivity as both are reversed with rapamycin treatment. mTOR is also phosphorylated in the resistant cell lines indicating that platinum resistance is associated with an increase in activity of this pathway. The mechanism of regrowth resistance in the platinum-resistant H69CIS200 and H69OX400 cells is a combination of activation of PI3K/Akt/mTOR signalling and alterations in control of the G1/S cell cycle checkpoint. However, more work remains to determine which factors in these pathways are governing this novel mechanism of platinum resistance.
Stordal, Britta. « Regrowth resistance in platinum-drug resistant small cell lung cancer cells ». Connect to full text, 2006. http://hdl.handle.net/2123/2467.
Texte intégralTitle from title screen (viewed 10 June 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Medicine, Faculty of Medicine. Degree awarded 2007; thesis submitted 2006. Includes bibliographical references. Also available in print form.
Brattström, Daniel. « Angiogenesis Related Markers In Non-Small Cell Lung Cancer ». Doctoral thesis, Uppsala University, Oncology, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3558.
Texte intégralThis thesis investigated the predictive and the prognostic powers of angiogenesis related markers in both operable and inoperable non-small cell lung cancer (NSCLC) patients.
In the first and second study, we investigated the serological fractions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 2 cohorts of patients with either operable or inoperable NSCLC.
Regarding operable NSCLC, we demonstrated significant correlations between VEGF and tumour volume and overall survival. Regarding bFGF, significant correlations with recurrent disease and survival were demonstrated. VEGF and bFGF correlated to each other and with platelet counts. In multivariate analysis, bFGF proved to be a significantly independent prognostic factor.
Regarding inoperable NSCLC, we demonstrated that patients with elevated bFGF levels before any treatment and during chemotherapy had a significantly poorer survival. During chemotherapy, each rise of one unit of bFGF (ng/L) corresponded to a 4 times increased risk of death. Regarding VEGF, elevated levels after radiotherapy corresponded with better survival. All prognostic information demonstrated in this study concerned patients with a, co-sampled, normal platelet count.
In the third study, three putative markers, HER-2, EGFR and COX-2, suitable for targeted therapies in resected NSCLC were investigated in a panel of 53 tumours and further investigated for a possible correlation with microvessel density. We demonstrated that HER-2 and COX-2 were mainly expressed in adenocarcinomas, whereas EGFR was only expressed in squamous cell carcinomas. COX-2 showed a trend towards a correlation with microvesssel density. The expression profile, HER-2+/EGFR-, was significantly correlated to poorer survival.
In the fourth study, a predictive model for recurrences consisting of p53, CD34 and CD105, and circulating serum fractions of VEGF and bFGF, was investigated. The two endothelial markers correlated with each other. CD105 expression correlated with p53 expression. No other significant correlations between markers could be demonstrated. A significant correlation between p53 overexpression and recurrent disease was demonstrated. The mutational status could not confirm the immunohistochemical correlation between p53 and recurrences.
In conclusion, the present thesis demonstrates that the angiogenic factors VEGF and bFGF analysed in sera have both predictive and prognostic information when measured in operable and inoperable NSCLC. Since HER-2 is overexpressed in NSCLC and linked with prognostic information, this marker might be a suitable target for therapy in NSCLC. Furthermore, in patients with operable NSCLC, p53 expression status was linked with recurrent disease and mean MVD.
Lam, Chi-leung David. « Gene expression profiling in non-small cell lung cancer ». Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38585777.
Texte intégralHo, Chung-man. « Non-small cell lung cancer from bench to bedside / ». Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39432592.
Texte intégralBerrieman, Helen Katherine. « Resistance to chemotherapy in non-small cell lung cancer ». Thesis, University of Hull, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415803.
Texte intégralFuron, Emeline. « Phenotypic variations and chemosensitivity in small cell lung cancer ». Thesis, Cardiff University, 2008. http://orca.cf.ac.uk/54491/.
Texte intégralOhri, Chandra. « The immune response to non-small cell lung cancer ». Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/8195.
Texte intégralHo, Chung-man, et 何重文. « Non-small cell lung cancer : from bench to bedside ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39432592.
Texte intégralLam, Chi-leung David, et 林志良. « Gene expression profiling in non-small cell lung cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38585777.
Texte intégralBryant, Jennifer. « Neuroendocrine and epithelial markers of small cell lung cancer ». Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/neuroendocrine-and-epithelial-markers-of-small-cell-lung-cancer(c7c51e2c-6443-4021-b2ff-469966cd10b6).html.
Texte intégralAgrawal, Vishesh. « Quantitative Imaging Analysis of Non-Small Cell Lung Cancer ». Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:27007763.
Texte intégralHolgersson, Georg. « Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC) ». Doctoral thesis, Uppsala universitet, Experimentell och klinisk onkologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-327925.
Texte intégralXinarianos, George. « Genetic alterations in non-small cell lung carcinomas ». Thesis, University of Liverpool, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343688.
Texte intégralChan, Kit-ying Loucia. « Expression analysis of Candidate cancer genes in non-small cell lung cancer / ». View the Table of Contents & ; Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38480360.
Texte intégralBaker, Amanda F., Neale T. Hanke, Barbara J. Sands, Liliana Carbajal, Janet L. Anderl et Linda L. Garland. « Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models ». BioMed Central, 2014. http://hdl.handle.net/10150/610318.
Texte intégral譚郭雅欣 et Gloria Tam. « Non-small cell lung cancer clinical trials on new medicines ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41711956.
Texte intégralDaly, Maria Catherine. « Chromosome 3 deletion mapping in human small cell lung cancer ». Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304095.
Texte intégralTai, Lai-shan. « Molecular genetic characterizations of human non-small cell lung cancer ». Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31375315.
Texte intégralCasadevall, Aguilar David. « Heterogeneity of biomarker expression in non-small cell lung cancer ». Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/457975.
Texte intégralThe success of precision medicine in oncology is dependent to a large extent on an adequate selection of patients who will receive targeted therapies aimed at specific molecular traits of their tumor. In order to be able conduct such patient selection, predictive biomarkers that can inform therapeutic decisions are essential. MET and PD-L1 are two relevant membrane receptors for non-small cell lung cancer (NSCLC) biology. MET is an oncogene the activation of which is involved in multiple pro-tumorigenic processes such as cell proliferation, motility and invasion. PD-L1 is a key molecule that acts during the immune response, and its overexpression in tumors is thought to mediate the ability of tumor cells to avoid immune cell recognition and destruction. Currently, there are specific therapies directed against these molecules. The most commonly used strategy to select the patients that will benefit from such drugs is the analysis of the expression of both molecules in tumor tissue. However, the value of MET and PD-L1 as predictive biomarkers and the method by which it should be determined is a subject of debate. Recent studies have detected a high degree of genomic heterogeneity in NSCLC tumor samples. This heterogeneity could significantly affect biomarker-based patient classification especially in the case of NSCLC, since biomarker studies are usually performed in small biopsies or cytology samples obtained through minimally invasive techniques. The main objective of the work presented in this thesis is to study the heterogeneity of the expression of MET and PD-L1 in NSCLC samples. For this purpose, we have analyzed tumor samples from NSCLC patients that had undergone surgical treatment at Hospital del Mar. Of each tumor, we have selected multiple geographically separate areas, which we analyzed independently. In the study evaluating MET, we selected four tumor areas per patient, while in the study evaluating PD-L1 we selected two areas. In each tumor area, we measured the expression MET and PD-L1 using immunohistochemical and fluorescence in situ hybridization methods (FISH). Finally, we compared the expression of MET and PD-L1 in different tumor areas. Regarding MET, we have found discordances between different tumor areas in 20-40% of cases using immunohistochemistry and in 25-50% of cases using FISH. Regarding PD-L1, this discrepancy was greater if we evaluated PD-L1 expression in tumor infiltrating lymphocytes (17-27%) than if we did so only in tumor cells (10-19%). Moreover, 36% of the cases with amplification of the gene coding for PD-L1 determined by FISH presented gene amplification only in one of the two areas analyzed. Overall, our results suggest that the expression of both biomarkers is heterogeneous, whether measured by immunohistochemistry or by FISH. This heterogeneity can have a potential impact on the classification of tumors based on the expression of biomarkers and, therefore, could represent a hurdle for the development of targeted therapies for NSCLC patients.
Tong, Wing-yee. « Studies on non-small cell lung cancer with EGFR mutation / ». View the Table of Contents & ; Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31495333.
Texte intégralCox, Giles. « Angiogenesis and matrix metalloproteinases in non-small cell lung cancer ». Thesis, University of Leicester, 2000. http://hdl.handle.net/2381/29608.
Texte intégralTai, Lai-shan, et 戴麗珊. « Molecular genetic characterizations of human non-small cell lung cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31375315.
Texte intégralTong, Wing-yee, et 唐穎儀. « Studies on non-small cell lung cancer with EGFR mutation ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45010432.
Texte intégralKoch, Andrea. « Clinical Aspects of Inflammation in Non-small Cell Lung Cancer ». Doctoral thesis, Linköpings universitet, Internmedicin, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-68749.
Texte intégralBrauneis, Alison Dooley. « Investigating the initiation and progression of small cell lung cancer ». Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/63063.
Texte intégralCataloged from PDF version of thesis.
Includes bibliographical references.
Small cell lung cancer (SCLC) comprises 18% of all lung cancer cases and is an aggressive disease with a five-year survival rate of less than 5%, mainly due to the advanced nature of the disease at the time of diagnosis. Despite the need to better understand this disease, the genetic lesions that contribute to SCLC remain poorly characterized. To investigate the genetic aberrations that occur in SCLC, we analyzed the copy number alterations in tumors and metastases arising in a mouse model of SCLC (mSCLC), driven by conditional inactivation alleles of two tumor suppressor genes, Trp53 and Rbl. We identified frequent, high-level amplification of a novel, protooncogenic transcription factor Nuclear Factor I/B (Nfib in mouse, NFIB in human), which frequently occurred coincident with amplification of a previously characterized oncogene, L-myc (Mycl). Functional studies revealed cooperation between Nfib and Lmyc in cellular transformation. Comparative genomics identified NFIB amplifications in human SCLC and uncovered a role for NFIB in regulating cell viability and proliferation. We also examined the effect of lung injury on SCLC initiation and progression utilizing naphthalene, a chemical that ablates the cells that line the bronchioles of the lung. The pulmonary neuroendocrine cells, the putative cell of origin of SCLC, are refractory to naphthalene-mediated injury. We demonstrated that naphthalene-mediated injury prior to tumor initiation in the mouse model of SCLC induced more advanced mSCLC lesions and decreased tumor latency. Throughout the course of this thesis work, we successfully utilized a mouse model of SCLC to interrogate the initiation of SCLC as well as to define the genetic alterations that occur in SCLC tumors and metastases. This work has led to the identification of candidate genes that promote tumor progression and to a better understanding of the process of tumor initiation. We anticipate that these findings will not only enhance our understanding of SCLC, but may lead to the development of therapeutics used to treat this aggressive disease.
by Alison L. Dooley.
Ph.D.
Kouverianou, Eleni. « Galectin-3 regulation of non small cell lung cancer growth ». Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17891.
Texte intégralUsó, Marco Marta. « ANALYSIS OF IMMUNOREGULATORY BIOMARKERS IN NON-SMALL CELL LUNG CANCER ». Doctoral thesis, Universitat Politècnica de València, 2015. http://hdl.handle.net/10251/51283.
Texte intégral[ES] El cáncer de pulmón es una de las principales causas de muerte relacionada con cáncer en el mundo, siendo el tercer tipo de cáncer más común. El cáncer de pulmón no microcítico (CPNM) representa casi el 85% de todos los cánceres de pulmón y la supervivencia a los 5 años va desde el 50% en estadios IA hasta el 15% en estadios IIIA. Hasta el momento, no se han descubierto biomarcadores capaces de predecir la progresión de la enfermedad en pacientes tanto en estadios resecables como en estadios avanzados, por lo que existe una clara necesidad de realizar estudios centrados en la búsqueda de biomarcadores pronósticos y diagnósticos en los diferentes tipos de muestra disponibles, como por ejemplo sangre, tejido fresco y tejido parafinado. El campo de la inmunología tumoral ha cambiado en la última década y actualmente se sabe que el sistema inmune juega un papel clave en cáncer. Las células inmunes que infiltran el tumor son un componente más del microambiente tumoral. Pese a que son potencialmente capaces de eliminar los antígenos tumorales, estas células no pueden evitar la formación y progresión tumoral. Esto es debido a que el tumor adquiere diversos mecanismos de regulación del microambiente tumoral con el objetivo de escapar del ataque del sistema inmune, como por ejemplo liberación de factores que impiden el correcto funcionamiento de los mecanismos de reacción inmune, modulación de vías co-estimuladoras y reclutamiento y activación de células inmunoreguladoras como las células T reguladoras, las células mieloides supresoras y los macrófagos asociados a tumores. El estudio de marcadores relacionados con la respuesta inmune y concretamente con los procesos de inmunoregulación puede proporcionarnos información pronóstica y predictiva relevante sobre los pacientes con cáncer. Por todo ello, el principal objetivo de esta tesis doctoral es analizar la presencia de marcadores relacionados con la inmunoregulación y evaluar su posible correlación con las variables clínico-patológicas y pronósticas en pacientes con CPNM mediante el uso de técnicas fiables y aplicables en la práctica clínica como la PCR cuantitativa y la inmunohistoquímica. Así mismo, esto nos permitirá conocer en mayor profundidad las características inmunológicas del microambiente tumoral en pacientes con CPNM.
[CAT] El càncer de pulmó és una de les principals causes de mort relacionades amb càncer al món, sent a més a més el tercer tipus de càncer més comú. El càncer de pulmó no microcític (CPNM) representa el 85% de tots els casos de càncer de pulmó aproximadament i la supervivència als 5 anys continua sent molt baixa. Fins el moment, no s'han descobert biomarcadors capaços de predir la progressió de la malaltia tant en pacients en estadis inicials com en estadis avançats. Per aquest motiu, existeix una clara necessitat de realitzar estudis centrats en la recerca de biomarcadors pronòstics i predictius en els diferents tipus de mostres disponibles, com per exemple sang, teixit fresc i teixit parafinat. El camp de la immunologia tumoural ha canviat en l'última dècada i actualment se sap que el sistema immune exerceix un paper clau en el càncer. Les cèl¿lules immunològiques que infiltren el tumour són un component més del microambient tumoural. Malgrat que aquestes cèl¿lules són potencialment capaces d'eliminar el antígens tumourals, s'ha evidenciat que no poden previndre la formació i progressió tumoural. Una de les raons per les quals s'observa aquest fenomen és que el tumour adquireix diversos mecanismes de regulació del microambient tumoural. Aquests mecanismes es basen en l'alliberació de factors que impedeixen el correcte funcionament del sistema immune, la modulació de vies coestimuladores i el reclutament i activació de cèl¿lules immunoreguladores com poden ser les cèl¿lules T reguladores, les cèl¿lules mieloides supressores i els macròfags associats a tumour. L'estudi de marcadors relacionats amb la resposta immune i més concretament amb els processos d' immunoregulació pot proporcionar informació pronòstica i predictiva rellevant sobre els pacients amb càncer. Per tot això, el principal objectiu d'aquesta tesi doctoral és analitzar la presència de marcadors relacionats amb la immunoregulació i avaluar la seva possible correlació amb les variables clinicopatològiques i pronòstiques de pacients amb CPNM mitjançant l'ús de tècniques fiables i aplicables a la pràctica clínica com són la PCR quantitativa i la immunohistoquímica. Així mateix, aquestes anàlisis ens permetran conèixer amb major profunditat les característiques immunològiques del microambient tumoural de pacients amb CPNM.
Usó Marco, M. (2015). ANALYSIS OF IMMUNOREGULATORY BIOMARKERS IN NON-SMALL CELL LUNG CANCER [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/51283
TESIS
Deskin, Brian J. « Histone deacetylase 6 functions in non-small cell lung cancer ». Thesis, Tulane University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10195328.
Texte intégralNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide in both men and women. Of relevance to our research presented herein are the Transforming growth factor β (TGF-β) signaling pathways and the heat shock response in the context of NSCLC. Dysregulation of TGF-β signaling often results in disease and is a common feature of many cancers including NSCLC where it governs cell fate and epithelial plasticity through the epithelial-to-mesenchymal transition (EMT). Another key feature of oncogenic TGF-β signaling is the crosstalk with other oncogenic pathways, like the NOTCH signaling pathway, which aids to restrict differentiation and modulates proliferation. Our research identified a mechanistic link between histone deacetylase 6 (HDAC6) and TGF-β1-induced Notch1 signaling. When HDAC6 is knocked down with siRNA or its deacetylase function is pharmacologically inhibited TGF-β1 activation of Notch signaling is abrogated. Within this paradigm we identified a protein complex consisting of HDAC6, heat shock protein 90 (HSP90), and the Notch1 receptor. In response to TGF-β1 stimulation, HDAC6 rapidly deacetylates HSP90 at lysine 294 which corresponds with cleavage and activation of Notch1.
Our investigations also uncovered a unique feature of HSP90 function in NSCLC. Activation of the heat shock response triggers activation of Notch1 signaling. We demonstrated that HDAC6 regulates this heat shock-induced Notch1 signaling through modulation of HSP90 function of cytoplasmic sequestration of the key transcription factor that governs the heat shock response, heat shock factor 1 (HSF1). Brief exposure of NSCLC cells to 42°C activates heat shock-induced Notch1 signaling, knockdown of HDAC6 with siRNA or pharmacological inhibition of HDAC6 abrogated this induction. In our investigations employing this combined strategy of targeting both HDAC6 and HSP90 we discovered that this treatment had an additive effect to enhance apoptotic markers and inhibit cell cycle progression in NSCLC cells. Individual HDAC6 or HSP90 inhibition slowed tumorigenesis and enhanced apoptosis of NSCLC in vivo. Taken altogether, our research identifies HDAC6 and HSP90 as regulators of key oncogenic pathways required for EMT and that combined inhibition of both these targets is a rational strategy to selectively kill NSCLC cells.
Tam, Gloria. « Non-small cell lung cancer clinical trials on new medicines ». Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41711956.
Texte intégralAcheampong, Emmanuel. « Assessment of circulating tumour cells in lung cancer patients ». Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2022. https://ro.ecu.edu.au/theses/2554.
Texte intégralBingula, Rea. « Non-small cell lung cancer, immunity and microbiota : laying ground for the gut-lung-lung cancer axis in human subjects ». Thesis, Université Clermont Auvergne (2017-2020), 2019. http://www.theses.fr/2019CLFAS009.
Texte intégralLung cancer is the main cause of death by cancer worldwide. Despite the variety of available treatments, including surgery, chemotherapy, radiotherapy, and immune therapy, the average 5-year survival is 60%. One of the underlying reasons is a very high variability in patients’ susceptibility to treatment, explained by genetic background and since recently – our microbiota. The term microbiota includes bacteria, archaea, fungi, viruses and protists that inhabit our organism. The studies in animal models show that the gut microbiota (focused on bacteria) has a crucial role in host’s responsiveness to therapy through the stimulation of immune system. In this light, several “communication axes” between the gut and distal tumour sites have started to develop, including the “gut-lung” axis. However, the resident microbiota in the lungs that could directly influence the tumour response and interact with the gut microbiota has been scarcely characterised. To enable further development of the idea of the “gut-lung-lung cancer” axis, we included 18 non-small cell lung cancer (NSCLC) patients eligible for surgery and analysed the microbiota from four different lung samples (non-malignant, peritumoural and tumour tissue and bronchoalveolar lavage fluid; BAL), saliva and faeces by high-throughput sequencing. We also analysed several immune markers, as lymphocytic tumour infiltrate, Th and neutrophil profiles and cytokines in BAL and blood, and inflammatory markers in faeces along with short-chain fatty acids. Focusing first on the lungs, we show that BAL microbiota represents a significantly distinct community compared to lung tissue microbiota by providing detailed characterisation of the four different lung samples. Since tumours in lower lobes are reported as the ones with the worse prognosis, we investigated how the lobe location affected the microbiota composition. Peritumoural tissue and BAL microbiota were identified as the most affected in both abundance and diversity, and tumour as the least affected. However, phylum Firmicutes, previously reported as elevated in chronic obstructive pulmonary disease compared to controls, was found more abundant in microbiota from lower lung lobes. Therefore, we propose that both increase in Firmicutes and extensive changes in peritumoural tissue could be associated to increased aggressiveness of the lower lobe tumours. Next, we show that the presence of metastatic lymph nodes (LN), negative prognostic marker in NSCLC, significantly influence the local tissue microbiota in relation to its respiratory profile. We reported that anaerobic bacteria were more abundant within the tumour in the presence of metastatic LN, and aerobic bacteria within the one without it. Moreover, exactly inverse was observed for the same bacteria in extratumoural tissues. Along with migratory hypothesis depending on the bacterial preference for growth conditions shaped by tumour’s features, we propose several biomarkers for detection of metastatic LN that might facilitate their detection without imposing LN biopsy. Finally, we showed that BAL microbiota is the most associated to the local immune response and independent of the presence of metastatic LN. Future research will focus on the exploration of the interaction between the lung microbiota, systemic immunity and the gut microbiota