Дисертації з теми "NSCLCs"
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Chater, Emily. "Novel therapeutic targets in NSCLC resistance to Erlotinib." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/50699.
Повний текст джерелаHolgersson, 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.
Повний текст джерелаStamatkin, Christopher W. "PHOSPHATIDYLINOSITOL 3-KINASE (PI3K) AS A THERAPEUTIC TARGET IN NSCLC." UKnowledge, 2014. http://uknowledge.uky.edu/pharmacy_etds/58.
Повний текст джерелаChatterjee, Saradiya. "Role of TLR7 in non-small cell lung carcinona (NSCLC)." Paris 6, 2013. http://www.theses.fr/2013PA066063.
Повний текст джерелаLung cancer accounts for over 1 million deaths per year with a 5-year survival of 8-12%. Stimulation of TLRs by the natural ligands like the PAMPs and DAMPs results in a proinflammatory signaling cascade. We have shown that stimulation of lung cancer cell lines with TLR7 agonist lead to tumor cell survival and chemoresistance in vitro. We studied the effect of TLR7 agonists on A549 and LL/2 cells injected in NOD/SCID and C57BL/6 mice either treated or not with cisplatin. Loxoribine has a pro-tumoral effect on A549 cells and induces chemoresistance in NOD/SCID mice. Blockade of TLR7 with IRS661 reversed the pro-tumoral effect of TLR7 agonist on A549 cells. CL264 was also found to have a pro-tumoral effect on LL/2 cells and induced chemoresistance in NOD/SCID mice. On the other hand CL264 at lower concentration induces an anti-tumoral effect on LL/2 cells while at a higher concentration demonstrated a pro-tumoral effect in C57BL/6 mice. We also demonstrated an overall bad prognostic value for higher expression of TLR7 by tumoral cells among NSCLC patients treated and not treated with neoadjuvant chemotherapy. These results suggest a pro- tumoral role and induction of chemoresistance by TLR7 in NSCLC patients. Use of TLR7 agonist as therapeutic option is recommended based on the TLR7 expression level for individual NSCLC patients. TLR7 antagonist holds promise for treatment of NSCLC in future
Recondo, Gonzalo. "Resistance Mechanisms to ALK Tyrosine Kinase Inhibitors (TKIs) in NSCLC." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS248/document.
Повний текст джерелаThe molecular study and classification of lung adenocarcinomas has led to the development of selective targeted therapies aiming to improve disease control and survival in patients. The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor from the insulin tyrosine kinase receptor family, with a physiologic role in neural development. Gene rearrangements involving the ALK kinase domain occur in ~3-6% of patients with lung adenocarcinoma. The fusion protein dimerizes leading to transactivation of the ALK kinase domain in a ligand-independent and constitutive manner. Lorlatinib is a third generation ALK inhibitor with high potency and selectivity for this kinase in vitro and in vivo, and elevated penetrance in the central nervous system. Lorlatinib can overcome resistance mediated by over 16 secondary kinase domain mutations occurring in 13 residues upon progression to first - and second - generation ALK TKI. In addition, treatment with lorlatinib is effective for patients who have been previously treated with a first and a second generation or a second generation ALK TKI upfront and is currently approved for this indication. The full spectrum of biological mechanisms driving lorlatinib resistance in patients remains to be elucidated. It has been recently reported that the sequential acquisition of two or more mutations in the kinase domain, also referred as compound mutations, is responsible for disease progression in about 35% of patients treated with lorlatinib, mainly by impairing its binding to the ALK kinase domain. However, the effect of these compound mutations on the sensitivity to the repertoire of ALK inhibitors can vary, and other resistance mechanisms occurring in most patients are unknown. My PhD thesis aimed at exploring resistance to lorlatinib in patients with ALK-rearranged lung cancer through spatial and temporal tumor biopsies and development of patient-derived models. Within the institutional MATCH-R study (NCT02517892), we performed high-throughput whole exome, RNA and targeted next-generation sequencing, together with plasma sequencing to identify putative genomic and bypass mechanisms of resistance. We developed patient-derived cell lines and characterized novel mechanisms of resistance and personalized treatment strategies in vitro and in vivo. We characterized three mechanisms of resistance in four patients with paired biopsies. We studied the induction of epithelial-mesenchymal transition (EMT) by SRC activation in a patient-derived cell line exposed to lorlatinib. Mesenchymal cells were sensitive to combined SRC and ALK co-inhibition, showing that even in the presence of an aggressive and challenging phenotype, combination strategies can overcome ALK resistance. We identified two novel ALK kinase domain compound mutations, F1174L/G1202R, C1156Y/G1269A, occurring in two patients treated with lorlatinib. We developed Ba/F3 cell models harboring single and compound mutations to study the differential effect of these mutations on lorlatinib resistance. Finally, we characterized a novel mechanism of resistance caused by NF2 loss of function at the time of lorlatinib progression through the development of patients derived PDX and cell lines, and in vitro validation of NF2 knock-out with CRISPR/CAS9 gene editing. Downstream activation of mTOR was found to drive lorlatinib resistance by NF2 loss of function and was overcome by providing treatment with mTOR inhibitors.This study shows that mechanisms of resistance to lorlatinib are more diverse and complex than anticipated. Our findings also emphasize how longitudinal studies of tumor dynamics allow deciphering TKI resistance and identifying reversing strategies
Baghai, Tabassom. "ATF3 as a Key Regulator of Cisplatin Cytotoxicity: Combining ATF3 Inducing Agents Enhances Cisplatin Activity in NSCLC." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37963.
Повний текст джерелаSouza, Cristiano de Pádua. "Perfil de expressão de microRNAs e seus alvos moleculares em carcinoma pulmonar." Botucatu, 2016. http://hdl.handle.net/11449/140150.
Повний текст джерелаResumo: Introdução: O câncer de pulmão é a principal causa de morte por câncer no mundo. Apesar dos avanços nas estratégias de diagnóstico e o desenvolvimento de novas terapias com alvos moleculares, pouco progresso tem sido observado quanto ao aumento de sobrevida dos pacientes. Portanto, a identificação de novos biomarcadores ainda é necessária para o desenvolvimento de novas terapêuticas para carcinomas pulmonares. Nesse contexto, os microRNAs (miRNAs) são moléculas promissoras, pois constituem uma classe de RNAs não-codantes reguladores da expressão gênica os quais têm sido evidenciados como biomarcadores diagnósticos, prognósticos e preditivos no câncer. Materiais e Métodos: Amostras de tecido pulmonar tumoral e normal de 38 pacientes com carcinoma de pulmão de células não pequenas (da sigla em inglês NSCLC), dos subtipos histológicos adenocarcinoma e carcinoma de células escamosas, foram avaliadas para a expressão global de miRNAs utilizando a plataforma TaqMan® Array Human MicroRNA card A v3.0 (Life Technologies). Os miRNAs com alterações na expressão (FC≥2,0) e p<0,05 foram considerados estatisticamente significativos. Os dados de expressão foram associados com a sobrevida global. Análises de bioinformática permitiram identificar genes-alvo regulados pelos miRNAs desregulados. A relação entre sobrevida global e a identificação de uma assinatura de expressão de miRNAs foi avaliada com objetivo de integrar nossos achados utilizando bancos de dados públicos. Resultados: Os resul... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor
Campbell, Thomas. "The role of voltage-gated sodium channels in non-small cell lung cancer." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-voltagegated-sodium-channels-in-nonsmall-cell-lung-cancer(a65f4c5e-b217-483b-91d3-bb669965eb03).html.
Повний текст джерелаBen, hamed Ibtissem. "Réponses cellulaires rapides de l’halophyte Cakile maritima au choc salin : analyse de leur implication dans la mort cellulaire programmée et l’adaptation." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS444.
Повний текст джерелаAbstractThis work aimed at understanding the specificity of cellular responses of the obligate halophyte Cakile maritima to salt shock and regulation of early events involved in programmed cell death and survival under salinity conditions. In a first step, we have shown that this plant is tolerant upon both repetitive salt shocks and gradual salt application. However, we have observed a cell death zones on older leaves subjected to a severe shock saline (400 mM NaCl). To better understand the cascade of events involved in the cell death process, we continued our experiments on suspension culture of C. maritima, which we have optimized ourselves the conditions for establishment and suspension culture of Arabidopsis thaliana (glycophyte model). In both species, salinity induced programmed cell death that depends on the duration and the intensity of the applied salt treatment. Also, the same cellular events, including depolarization of the plasma membrane due to the Na+ influx by NSCCs, mitochondrial dysfunction, production of superoxide anions and activation of caspase-like proteins, occurs early in response to salt stress. C. maritima tolerance to salt stress is potentially due to a strong accumulation of ascorbate that would allow this halophyte to better reduce damage generated by oxidative stress. C. maritima is also distinguished by a better ability to control the cytoplasmic accumulation of Na+, leading to the survival of its cells under salinity conditions. This study on cell death induced by NaCl in cell culture of C. maritima also allowed us to identify two types of behavior in this population of cells in culture: one related to a sustained depolarization in response to NaCl probably leading to death of these cells, the other linked to a transient depolarization indicating that the Na+ influx through the NSCC was probably regulated allowing cells exhibiting this behavior to survive by avoiding excessive accumulation of Na+ in the cytosol. In the last part of this work, we have demonstrated the ability of C. maritima to exclude Na+ via the SOS system. This result suggests the existence of a second signaling pathway induced in parallel to that leading to cell death. This pathway, involving a rapid production of singlet oxygen, could allow a Ca2+ influx in the cytoplasm that acts as an elicitor for activation of SOS3 protein and SOS2-SOS1 cascade and H+- ATPases of the plasma membrane allowing Na+ efflux via SOS1 out of cells
Schaal, Courtney. "Regulation of nAChRs and Stemness by Nicotine and E-cigarettes in NSCLC." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6582.
Повний текст джерелаSarin, Navin [Verfasser]. "Cisplatin resistance is associated with altered signalling in NSCLC cells / Navin Sarin." Bonn : Universitäts- und Landesbibliothek Bonn, 2018. http://d-nb.info/1153467119/34.
Повний текст джерелаPetroff, Alev [Verfasser], and Christian [Akademischer Betreuer] Rübe. "Langzeitergebnisse radikal behandelter synchron vs. metachron oligometastasierter NSCLC / Alev Petroff ; Betreuer: Christian Rübe." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1175950270/34.
Повний текст джерелаParikh, Ravi B. "DEFINITIVE PRIMARY THERAPY IN PATIENTS PRESENTING WITH OLIGOMETASTATIC NON-SMALL CELL LUNG CANCER (NSCLC)." Thesis, Harvard University, 2014. http://etds.lib.harvard.edu/hms/admin/view/47.
Повний текст джерелаBalko, Justin M. "THE PHARMACOGENOMICS OF EGFR-DEPENDENT NSCLC: PREDICTING AND ENHANCING RESPONSE TO TARGETED EGFR THERAPY." Lexington, Ky. : [University of Kentucky Libraries], 2009. http://hdl.handle.net/10225/1062.
Повний текст джерелаTitle from document title page (viewed on September 17, 2009). Document formatted into pages; contains: viii, 175 p : ill. (some col.). Includes abstract and vita. Includes bibliographical references (p. 103-123).
Koch, Franziska [Verfasser]. "Humanes ex-vivo Lungentumormodell : Nutzung für Temperaturmessungen während der Thermoablation von NSCLC. / Franziska Koch." Greifswald : Universitätsbibliothek Greifswald, 2011. http://d-nb.info/1018242198/34.
Повний текст джерелаRamos, Alexis. "Cancer Genome Characterization with SNP Array and Whole-Exome Sequencing Analysis." Thesis, Harvard University, 2011. http://dissertations.umi.com/gsas.harvard:10036.
Повний текст джерелаUsó, 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.
Повний текст джерела[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
Schneeberger, Valentina. "Novel Roles of the Protein Tyrosine Phosphatase SHP2 in Non-small Cell Lung Cancer." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5306.
Повний текст джерелаReuter, Cécile [Verfasser]. "Mutationsabhängige Aktivität von niedermolekularen reversiblen und irreversiblen Inhibitoren der EGFR Signalkaskade in NSCLC / Cécile Reuter." Köln : Deutsche Zentralbibliothek für Medizin, 2012. http://d-nb.info/1026215080/34.
Повний текст джерелаReinert, Christian Philipp [Verfasser]. "Einfluss von Lipoteichonsäuren von Staphylococcus aureus auf die Proliferation von NSCLC-Zelllinien / Christian Philipp Reinert." Gießen : Universitätsbibliothek, 2017. http://d-nb.info/1130119807/34.
Повний текст джерелаTam, Yee-san Issan, and 譚薏珊. "Epidermal growth factor receptor (EGFR) mutations and phosphorylation pattern in non-small cell lung cancer (NSCLC)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40687673.
Повний текст джерелаBertram, Veit [Verfasser], and Rainer M. [Akademischer Betreuer] Bohle. "Quantitative Expressionsanalyse von TTF-1 in NSCLC und pulmonalen Metastasen / Veit Bertram ; Betreuer: Rainer M. Bohle." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2019. http://d-nb.info/1197612076/34.
Повний текст джерелаLane, Keara M. "Negative feedback regulation as a means to constrain the oncogenic potential of mutant Egfr in NSCLC." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68427.
Повний текст джерелаCataloged from PDF version of thesis. Vita.
Includes bibliographical references.
The discovery of EGFR kinase domain mutations in NSCLC patients who responded to tyrosine kinase inhibitors (TKIs) represented the first example of a targeted therapy for lung cancer. The dependence of these human tumors on sustained mutant receptor expression for survival, together with the discovery that ectopic expression of the receptor resulted in transformation, suggested that these mutations are causal events, and as such would be sufficient to induce tumor formation in the lung. To investigate this, and to further our understanding of how deregulated signaling through the mutant receptor could initiate tumor formation, we generated both a conditional and constitutive knock-in allele of one such mutation, L858R, at the endogenous murine Egfr locus. Expression of mutant Egfr failed to induce lung tumors in these mice; further analysis of the germline mutant mice revealed significant downregulation of the mutant receptor, and this was predominantly at the post-transcriptional level. These data suggest that normal cells can respond to an oncogenic lesion by upregulating negative feedback pathways to counteract the induction of aberrant signaling, and disabling these feedback mechanisms may be an essential component of the progression of EGFR mutant tumors. A multitude of positive and negative feedback loops converge on signaling pathways to ensure the appropriate output in response to a given stimulus. The role of oncogenes is typically thought of in terms of increasing the output of a signaling pathway, and while the contribution of the associated negative feedback loops is no doubt important, they have been afforded little attention. Recent studies have highlighted the existence of negative feedback mechanisms in established tumors and the integral role they play in shaping the signaling network, with a corresponding appreciation for how such feedback loops can profoundly influence therapeutic response. The capacity of negative regulators to modulate the oncogenic potential of a mutant protein in the context of tumor initiation has rarely been examined. Using a doxycyclineinducible system we recapitulate the aforementioned downregulation of mutant Egfr, initially observed in both tissues and MEFs derived from EgfrL858R mutant mice, in an ectopic cell culture expression system. We establish a role for ERK pathway signaling, and specifically DUSP6, in receptor degradation, and solidify the role of the E3 ligase, CULLIN5, in the downregulation of the mutant receptor. The existence of these negative feedback loops may explain the observation that mutation of EGFR is often coincident with gene amplification in NSCLC, and suggest that such amplification may primarily serve as a means to counteract the downregulation. The amplification of oncogenes is a recurring feature of many human tumors, but the contribution of gene amplification to particular stages of tumor development, or the molecular requirements for amplification to occur are unknown. EGFR is mutated and coincidentally amplified in NSCLC, but the relative contribution of mutation and amplification, both to tumor phenotype and therapeutic sensitivity, is not clear. The inability to model amplification in the mouse has contributed significantly to our limited mechanistic understanding of how gene amplification occurs in tumors. Using a yeast endonuclease, -Scel, and an allele that contains target sites for this enzyme engineered telomeric to mutant Egfr on chromosome 11, we attempted to initiate breakage-fusion-bridge (BFB) cycles in the lung, as these are thought to be a precursor to gene amplification. Our inability to elicit tumor formation using this strategy highlights the limitations in our understanding of how amplicons form in human tumors or the particular context required. While it would provide tremendous insight into mutant EGFR tumor development, a model of targeted gene amplification has thus far eluded us, and remains one of the significant challenges facing the mouse modeling community.
by Keara M. Lane.
Ph.D.
Abdo, Mustafa [Verfasser]. "Prediction of patients’ response to immune checkpoint inhibitors in the treatment of advanced NSCLC / Mustafa Abdo." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1228623848/34.
Повний текст джерелаStorti, Camila Baldin. "Perfil de expressão de genes associados aos telômeros em carcinoma pulmonar de células não pequenas (NSCLC)." Botucatu, 2018. http://hdl.handle.net/11449/153294.
Повний текст джерелаResumo: O câncer de pulmão é o câncer que apresenta maior mortalidade no mundo: >1,6 milhões de óbitos por ano segundo a Organização Mundial de Saúde (OMS), sendo o câncer de pulmão de células não pequenas (NSCLC) o tipo mais frequente (~ 85%) de carcinoma pulmonar. O NSCLC apresenta dois subtipos histológicos principais: adenocarcinoma (LUAD) e carcinoma de células escamosas (LUSC). Pesquisas têm sido realizadas objetivando identificar biomarcadores moleculares úteis como alvo terapêuticos em NSCLC e os telômeros têm sido considerado alvos promissores para terapias antitumoral, devido ao seu papel crucial na integridade, estabilidade e manutenção genômica. Telômeros humanos consistem em DNA repetitivo rico em G associado a proteínas do complexo shelterin e mantido pela ação da telomerase. Estudos recentes mostraram que a expressão de TERT (subunidade catalítica da telomerase) e de alguns componentes do complexo shelterin estão alterados em câncer de pulmão. No entanto, a correlação entre alterações na função telomérica e o desenvolvimento e progressão de NSCLC não foi elucidada. Portanto, o objetivo do presente estudo foi verificar alterações na expressão de genes associados aos telômeros, incluindo os ncRNAs associados à regulação e manutenção dos telômeros em NSCLC, no intuito de identificar novos biomarcadores associados ao desenvolvimento e progressão do NSCLC. Para tanto, foram realizadas análises de expressão de 50 genes associados aos telômeros em amostras de tecido tumoral e... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: According to the World Health Organization, lung cancer has a high mortality rate associated with >1.6 million deaths per year, being Non-small cell lung cancer (NSCLC) the most frequent type (~ 85%) of lung carcinoma. Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two major histological subtypes of NSCLC. Research efforts have been made to identify molecular biomarkers useful as therapeutic targets in NSCLC and telomere have been considered very promising targets for anticancer therapies due to their crucial role in genome integrity maintenance and stability. Human telomeres consist of repetitive G-rich DNA associated with proteins of the shelterin complex, maintained by the action of telomerase. Recent studies showed that expression of TERT (telomerase reverse transcriptase component) and of some of the shelterin components are altered in lung cancer. However, the mechanisms of telomere deregulation associated with NSCLC development and progression have not been elucidated. Therefore, our aim was to study expression changes affecting telomere-associated genes and ncRNAs associated with telomere regulation and maintenance in NSCLC. Such alterations may represent novel biomarkers associated with NSCLC development and progression. For this purpose, expression analyzes of 50 telomere-associated genes were performed in samples of tumor tissue and normal lung tissue, adjacent to the tumor, from patients with NSCLC. The following techniques were used: 1... (Complete abstract click electronic access below)
Mestre
Wang, Yu-Chieh. "Exploitation and Mechanistic Validation of Drug-combination Strategies to Overcome EGFR-inhibitor resistance in NSCLC cells." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1226515990.
Повний текст джерелаTam, Yee-san Issan. "Epidermal growth factor receptor (EGFR) mutations and phosphorylation pattern in non-small cell lung cancer (NSCLC)." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40687673.
Повний текст джерелаArthur, Muller [Verfasser], and Ursula [Akademischer Betreuer] Nestle. "Prospektive Evaluation des Verhaltens der Tumorgewebe bei NSCLC in der FDG-PET unter Strahlentherapie (Response PET/CT)." Freiburg : Universität, 2018. http://d-nb.info/1220225428/34.
Повний текст джерелаLinsel, Sören [Verfasser]. "Experimentelle Untersuchungen zum Proliferationsverhalten von NSCLC-Zelllinien unter Endotoxin-Stimulation : die Rolle des Cyclooxygenase-Metabolismus / Sören Linsel." Gießen : Universitätsbibliothek, 2016. http://d-nb.info/1102154792/34.
Повний текст джерелаMakowiecki, Christina Michaela [Verfasser]. "Potential der siRNA-Transfektion auf chemotherapieresistente NSCLC- und Pleuramesotheliomzellen - Auswirkungen auf Viabilität und Wachstumsverhalten / Christina Michaela Makowiecki." Tübingen : Universitätsbibliothek Tübingen, 2021. http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1191334.
Повний текст джерелаKhaddam, Sinan M. D. "Difference in outcomes between central airway lesions requiring stents and lesions that donot in patients with NSCLC." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553513958608363.
Повний текст джерелаSchulze, Arik Bernard [Verfasser], and Rainer Gerhard [Akademischer Betreuer] Wiewrodt. "Das RhCE-Protein beeinflusst die Prognose von Patienten mit NSCLC / Arik Bernard Schulze ; Betreuer: Rainer Gerhard Wiewrodt." Münster : Universitäts- und Landesbibliothek Münster, 2016. http://d-nb.info/1140588087/34.
Повний текст джерелаRoesner, Anuschka Josphine [Verfasser], and Gian [Akademischer Betreuer] Kayser. "Einfluss der PD-L1-Expression sowie von tumorinfiltrierenden Lymphozyten auf das Ansprechen von Immuncheckpoint-Inhibitoren im NSCLC." Freiburg : Universität, 2019. http://d-nb.info/1212795601/34.
Повний текст джерелаMaurin, Pauline. "Caractérisation fonctionnelle du complexe LKB1/STRADß au cil primaire et les conséquences au cours de la tumorigenèse." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5065.
Повний текст джерелаSTK11 gene mutations were originally identified as responsible for the Peutz-Jeghers syndrome of which severity is mainly related to an increase incidence of tumor development. The product of this gene the serine/threonine kinase LKB1 gets its activity or its expression reduced, sometimes even lost, following somatic mutations in several types of cancer such as pancreas, liver but mainly from lung. Indeed, almost 30% of non-small cell lung carcinoma (NSCLC) does not express anymore or only an inactive form, has led to consider this kinase as tumor suppressor of importance. While there is no doubt of the involvement of its catalytic activity molecular mechanisms responsible for its tumor suppressor properties remain to be identified. Indeed, whereas its function as regulator of cellular metabolism through AMPK has been favor for a while, it is currently re-assess to benefit to its regulator function on canonical Wnt signaling. My thesis work, reinforce this eventuality in NSCLC. Indeed, among the two functional complexes formed by LKB1 through its association with STRADα or β pseudokinases, my results show that only the complex related to STRADβ is involved in the canonical Wnt pathway regulation. For that, LKB1/STRADβ complex localizes at primary cilia and participates to MARK3 kinase activation. These results strengthened by a STRADβ knockout mouse model and an a posteriori transcriptomic analysis of lung adenocarcinoma patient datasets related to their clinical records, suggest that LKB1 tumour suppressor activity is associated with its localization and its function at primary cilia participating in the activation of MARK3 and thus regulation of canonical Wnt signaling
Huscher, Stefan. "Retrospektiver Vergleich der Behandlungsergebnisse konventioneller Resektionstechniken des NSCLC im Stadium Ia/Ib mit Lasersegmentresektionen unter Anwendung eines neu entwickelten 1318nm Nd:YAG-Lasers." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1213965283337-04328.
Повний текст джерелаMüller, Benedikt Felix [Verfasser], and Ursula [Akademischer Betreuer] Klingmüller. "Interactions of EGFR/IGF-1R Signaling in NSCLC - A Systems Biology Approach / Benedikt Felix Müller ; Betreuer: Ursula Klingmüller." Heidelberg : Universitätsbibliothek Heidelberg, 2015. http://d-nb.info/1180501160/34.
Повний текст джерелаSeiz, Julia Raphaela [Verfasser]. "Rac1b-spezifische Effekte und Auswirkungen der 3D-Kultivierung auf Differenzierung und Signaltransduktion in NSCLC-Zelllinien / Julia Raphaela Seiz." Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1199264474/34.
Повний текст джерелаKurian, Stefanie [Verfasser]. "Effects of combination therapy of PDE5 inhibitor sildenafil and multikinase inhibitors sorafenib and sunitinib in NSCLC / Stefanie Kurian." Gießen : Universitätsbibliothek, 2015. http://d-nb.info/1076760546/34.
Повний текст джерелаPamarthi, Pavan Kumar [Verfasser]. "Role of prostanoid receptor EP1 in the progression of non-small cell lung cancer (NSCLC) / Pavan Kumar Pamarthi." Gießen : Universitätsbibliothek, 2013. http://d-nb.info/106518395X/34.
Повний текст джерелаMüller, Benedikt [Verfasser], and Ursula [Akademischer Betreuer] Klingmüller. "Interactions of EGFR/IGF-1R Signaling in NSCLC - A Systems Biology Approach / Benedikt Felix Müller ; Betreuer: Ursula Klingmüller." Heidelberg : Universitätsbibliothek Heidelberg, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-191984.
Повний текст джерелаJaber, Almahdi. "Oncogene driver mutations and copy number variation as markers for predicting drug resistance and disease outcome in NSCLC." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/39168.
Повний текст джерелаBesson, Florent. "Integrating PET-MR data for a multiparametric approach of tumour heterogeneity in non-small-cell lung cancer (NSCLC)." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS081.
Повний текст джерелаTumor heterogeneity is an important factor of progression and resistance to treatment. Multiparametric PET-MRI imaging offers unique opportunities to characterize biological cellular processes, but has never been evaluated at the regional level in Non-Small Cell Lung Cancer (NSCLC), the leading cause of oncological death. A simultaneous dynamic multiparametric 18F-FDG PET-MRI approach has been developed to this end. This approach required the “in-house” implementation of the reference absolute PET quantitative method of glucose metabolism (Sokoloff's tri-compartmental model); the development of a method for correcting geometric distortions in diffusion weighted imaging, validated on phantom and clinically tested; the phantom validation of quantitative MRI methods (T1/T2 relaxometry), also clinically tested; and the "in-house" implementation of the Tofts compartmental model (extended version) for the evaluation of tumor vascularization by dynamic perfusion MRI. The results of our work, performed at the regional intra-tumor level, illustrate the heterogeneity of the regional interlinks between glucose metabolism and vascularization in NSCLC, two fundamental biological hallmarks of tumor progression, and show that an unsupervised tumor partitioning by Gaussian mixture model, integrating all the PET-MRI biomarkers of this project, individualizes 3 types of supervoxels, whose biological signature can be predicted with 97% accuracy by 4 dominant PET-MRI biomarkers, revealed by metaheuristic machine learning methods
Seiz, Julia [Verfasser]. "Rac1b-spezifische Effekte und Auswirkungen der 3D-Kultivierung auf Differenzierung und Signaltransduktion in NSCLC-Zelllinien / Julia Raphaela Seiz." Gießen : Universitätsbibliothek, 2019. http://d-nb.info/1199264474/34.
Повний текст джерелаSamek, Melanie [Verfasser]. "Erlotinib beim fortgeschrittenen nichtkleinzelligen Lungenkarzinom (NSCLC) : klinische Evaluation im Rahmen einer Phase IV Studie (Tarceva EAP) / Melanie Samek." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2010. http://d-nb.info/1004771843/34.
Повний текст джерелаYang, Zheng. "Anti-cancer synergy of targeting pyruvate dehydrogenase kinase 1 (PDK1) in combination with EGFR-TKi in NSCLC therapy." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953612.
Повний текст джерелаKurtyka, Courtney A. "Novel Therapeutic Strategies in Lung Cancer." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5363.
Повний текст джерелаKrüger, Marcus. "Molekulare und funktionale Charakterisierung der neuronalen bHLH Transkritptionsfaktoren NSCL-1 und NSCL-2." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=969337183.
Повний текст джерелаYu-Hsin and 黃育新. "Genetic determinants of ALIMTA sensitive and resistant in NSCLCs." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/31082657452910897484.
Повний текст джерела中山醫學大學
醫學分子毒理學研究所
97
Pemetrexed(alimtaR)has been approved for second and first-line treatment in non-small cell lung cancer (NSCLC) patients. There are many NSCLC patients resistance to ALIMTA. However, there is still lacking of clinical biomarkers for predicting the therapeutic response of ALIMTA. Clinical implication and future perspectives of molecular markers were in the detection of circulating cancer cells of patients with malignancy. In in vitro, expression of metastasis molecular, migration, invasion and growth inhibition has been observed between durg-sensitive cells and durg-resistant cells following exposure to ALIMTA. Human NSCLC cell lines, with variable expression of the known molecular determinants of ALIMTA sensitivity, were exposed to ALIMTA using different dose. Antitumor effect was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle distribution by flow cytometry, and expression of cell cycle mediators by Western blot. The metastasis was determined by median effect analysis. Migration and invasion by Boyden chamber, wound healing assay, gelatin zymography. When cells were exposed to ALIMTA, the differant cytotoxic effect was observed in drug-sensitive A549 cell lines and drug-resistant H1355 cell lines. As a consequence of the increase in p53 protein, nm23-H1 protein and mRNA were up-regulated expression in following exposure to ALIMTA from A549 cells. ALIMTA treatment determined a significant up-regulation Lipocalin2 in protein and mRNA in A549 cells, and did not significantly affect the levels of Lipocalin2 mRNA in H1355 cells. Further, RNA interference (RNAi)-mediated Lipocalin2 and nm23-H1 down-regulation generated sensitility and metastases to ALIMTA in A549 cells. When p53 expression was inhibited by RNA interference in adenocarcinoma cell line A549 (A549-p53i cells), cells had a highest motility. But Cells lacking of p53 were also more sensitive to ALIMTA treatment by migration assay. Lipocalin2 inhibition would decrease the mobitity of A549 cells. Until 2 μM ALIMTA treatment, the migration would be reduced in lipocalin2 silensing A549 cells. Moreover, nm23-H1 inhibition would induce the mobitity of A549 cells, more resistant to ALIMTA treatment by migration assay. ALIMTA increases p27KIP1 and p21CIP1/WAF1 binding to cyclinA-CDK2 complexes and inhibits cyclinA activity in A549 cells. P21CIP1/WAF1 and p27KIP1 are able to arrest the growth of cells in the G1 phase of the cell cycle. In conclusion ALIMTA could play a role as a genetic determinant of ALIMTA sensitive and resistant in NSCLCs.
Lee, Yi-Fang, and 李伊芳. "How TGF-beta triggers the production of ALDH3A1 to protect NSCLCs (H460) from oxidative stress." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/t85j5k.
Повний текст джерела國立中興大學
生命科學系所
102
About 80% of all lung cancers are non-small cell lung cancers (NSCLCs), their high fatal rate is often attributed to the development of drug resistance of these cells. To understand the underlying mechanisms responsible for the drug resistance of NSCLCs may help to design new drugs or therapeutic regimens for the control of this disease. The main goals of the thesis were to confirm the anti-oxidative role of aldehyde dehydrogenase 3A1 (ALDH3A1) in the development of TGF-beta resistance of NSCLC cells (H460) and to delineate the underlying signaling pathway responsible for TGF-beta-induced ALDH3A1 production. Results showed that H460 cells were resistant to but CH27 cells were susceptible to TGF-beta induced growth inhibition. The activity and protein level of ALDH3A1 were higher in H460 cells than that in CH27 cells. TGF-beta can further increase the protein expression and activity of ALDH3A1 of H460 cells whereas showed no effect on that of CH27 cells. DEAB (ALDH3A1 inhibitor) inhibited not only the activity of ALDH3A1, the survival of H460 cells against TGF-beta, indicating the presence or increase of ALDH3A1 was important for the survivals’ development of TGF-beta resistance of H460 cells. The ROS released form H460 cells was lower than that of CH27 cells;that ALDH3A1 can help to remove excessive ROS from cells. Our results however, showed that TGF-beta treatment (24h) can reduce the release of ROS and protect the survival of H460 cells;in the presence of DEAB (ALDH3A1 inhibitor), TGF-beta-induced effects were both interrupted;indicating TGF-beta was capable of promoting the production, then release of ROS from H460 cells, which however was inhibited by ALDH3A1 (also triggered by TGF-beta). When H460 cells were given excessive amount of H2O2 (1mM or 2mM), DEAB exacerbated the H2O2-caused cell damage whereas TGF-beta protected cells against H2O2 insult, and TGF-beta-mediated cell protection was again blocked by DEAB. When H460 cells were treated with t-BuOOH (50μM;24h), the release of intracellular ROS was increased;TGF-beta co-treatment not only reduced the ROS release but also increased the survival of t-BuOOH-treated H460 cells. These results further demonstrated that TGF-beta-induced ALDH3A1 can protect H460 cells against extracellular and highly possible the intracellular oxidative stress also to increase the survival rate and drug resistance. Western blotting and chemical blocking strategy were also used to further delineate the underlying signaling pathway responsible for TGF-beta-induced ALDH3A1 production. The results for the first time showed that TGF-beta activated the PPAR-gamma/Akt pathway to stimulate the protein expression of ALDH3A1 in H460 cells, the involvements of EGFR, ERK and NF-kappa B were however, excluded. In overall, TGF-beta can act through PPAR-gamma/Akt pathway to stimulate the expression of ALDH3A1, which played a critical role in the protection of H460 cells against both extracellular and intracellular oxidative stress, that further elevated the survival and drug (TGF-beta) resistance of H460 cells. Luck of ALDH3A1 induction (such as in CH27 cells) may render the cells to be TGF-beta susceptible. ALDH3A1 therefore can be viewed as an index for drug resistance and also as a potential target for the diagnosis and/or therapeutic treatments of NSCLCs with drug resistance. ALDH3A1 inhibitor (DEAB), PPAR-gamma inhibitor (GW9662) or Akt inhibitor (LY294002), consequently may all have their values in disruption of the drug resistance and survival of H460 cells by inhibiting the ALDH3A1 production. At present, GW9662 and DEAB have been proven to do so. The anti-cancer effect of DEAB, GW9662 and LY294002, therefore is worthy of further investigation in both in vitro and tumor-heaving animal models in near future.
Lin, Li-Chiung, та 林麗瓊. "Role of PPARγ in the development of TGFβ resistance of NSCLCs (H460): in vitro and in vivo study". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/7ehb54.
Повний текст джерела國立中興大學
生命科學系所
99
The primary goal of the study was to understand the molecular mechanism responsible for the development of drug resistance of non-small cell lung cancer (NSCLC) cell, H460, against transforming growth factor β (TGFβ). The role of peroxisome proliferator-activated receptor γ (PPARγ) in disabling the tumor suppressing effect whereas promoting the metastasizing effect of TGFβ on H460 cells were the first two major issues to be approached followed by signaling pathways identification. A novel tumor mouse model using a group of middle aged BALB/c mice implanted with H460 xenograft tumor cells has also been established to further examine the development and metastasis of H460 cells within the animal body and to screen for anti-cancer drug for control of H460 cells in vivo. Our results showed the H460 cells revealed a drug resistance to TGFβ after the short or long term drug exposure. TGFβ-induced PPARγ was able to interact with and prevent the nuclear infiltration of Smad3/p-Smad3 that subsequently disrupt TGFβ-induced mitoinhibition in H460 cells and led to TGFβ resistance. TGFβ was later found can act through P38 and/or β-catenin signaling pathway to trigger the expression of PPARγ, which was also critical for TGFβ-induced epithelial to mesenchymal transition (EMT) and metastasis of H460 cells. PPARγ could activate the epidermal growth factor receptor (EGFR)/c-mesenchymal-epithelial transition factor (c-MET) pathway to decrease the expression of E-cadherin, or interact with β-catenin and promote its nuclear infiltration, either way might contribute to the EMT and metastasis of H460 cells induced by TGFβ. PPARγ was shown to have a positive reciprocal interaction with β-catenin. GW9662 (PPARγ inhibitor) and PPARγ-specific shRNA both revealed a therapeutic value in the control of H460 cells by breaking of PPARγ-protected cell growth and TGFβ-induced/PPARγ-mediated metastasis of H460 cells. The therapeutic value of GW9662 in the control of H460 cells-derived tumor was further confirmed in vivo by using the tumor mouse model has just described above. In addition to the tumor suppressive effect, GW9662 also inhibited the lung inflammation in H460 cells-implanted mice. This anti-inflammatory effect, however, might be due to GW9662-caused tumor inhibition of H460 cells. The novelty of our newly-developed tumor mouse model was that, human H460 cells were able to grow in immunocompetent mice instead of nude or SCID mice (immunodeficient). In brief, the decline of neutrophil activity in middle aged mouse was critical for the development of H460 xenograft in lung whereas the increase of macrophage activity was critical for the growth of murine-derived tumor. H460 xenograft tumor, on the other hand, might further decrease neutrophil activity to favor the tumor growth, and be the reason to cause pulmonary inflammation in H460-bearing mice. In overall, PPARγ was for the first time being addressed in H460 tumorigenesis and its drug resistance to TGFβ. The growth protecting and metastasis promoting effects of PPARγ in H460 cells have suggested that PPARγ may be a good molecule target to be approached in target therapy for many drug resistant-cancer cells such as H460. The therapeutic value of GW9662 in the control of H460 cells both in vitro and in vivo further supported this notion.