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Die Analyse der Neoangiogenese anhand des Vergleichs der CD31-und PEDF-Expression im vitalen Gewebe des Adeno-und Plattenepithelkarzinoms der Lunge / Characterization of neoangiogenesis by CD31 and PEDF expression profiling in non-small cell lung cancerOellerich, Angelika 13 December 2016 (has links)
Das Lungenkarzinom ist weltweit die häufigste Krebstodesursache. Ein möglicherweise erfolgsversprechender Angriffspunkt in der Therapie stellt die Tumorangiogenese dar, welche sich immunhistochemisch quantifizieren lässt. In der vorliegenden Arbeit wurde CD31, welcher als Marker für vorhandene Neoangiogenese fungiert, sowie PEDF als Antiangiogensesfaktor beschrieben und deren Einfluss auf die Gefäßbildung untersucht.
Die Zielsetzung der Arbeit war es zu untersuchen, ob Unterschiede im Expressionsmuster bei einem Plattenepithel- und Adenokarzinom der Lunge zu sehen sind, ob eine Korrelation in der Expression von CD31 und PEDF zu erkennen ist und ob eine Aussage zur Prognose anhand der Expression möglich ist. Das Kollektiv umfasste klinisch anotierte Proben von 42 Patienten mit einem Plattenenpithelkarzinom der Lunge und 27 Patienten mit einem Adenokarzinom der Stadien Ia-IIIB.
Sowohl die CD31 als auch die PEDF-Expression waren zwischen den Tumorentitäten nicht signifikant unterschiedlich. Im Expressionsvergleich von CD31 und PEDF zeigte sich beim Kollektiv der Plattenepithelkarzinome eine signifikante negative Korrelation bezogen auf CD31 und PEDF, gemessen anhand der Intensität. Beim Kollektiv der Adenokarzinompatienten zeigt sich eine positive Korrelation bezogen auf das CD31-Signal und der PEDF-Fläche. Für die Untersuchung zur Überlebensanalyse wurde das Kollektiv der Patienten, welche an einem Plattenepithelkarzinom erkrankt waren betrachtet. Die in der Literatur beschriebenen klassischen Einflussgrößen wie Tumorgröße, Lymphknotenstatus und Tumorstadieneinteilung auf die Überlebensraten konnten in dieser Arbeit bestätigt werden, allerdings erbrachte lediglich die Untersuchung der Tumorgröße eine statistisch signifikante Aussage. Hier konnte gezeigt werden, dass Patienten mit einem pT1-Tumor eine deutlich bessere Überlebensprognose haben als Patienten mit einem Tumor der Größe T2 oder größer (p=0.029). In der vorliegenden Studie ergab eine hohe CD31-Expression ein statistisch signifikant besseres Überleben der Patienten mit einem Plattenepithelkarzinom (p=0.038). Die 5JÜR der Patienten mit hoher CD31-Expression beträgt 67%, die mit niedriger 37%. Die Untersuchungen zur PEDF-Fläche als auch zur PEDF-Intensität ergaben keine Korrelation auf das Überleben und somit auf die Prognose.
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Adaptive Radiation Therapy for Lung CancerDial, Christian W 01 January 2014 (has links)
Prognosis for lung cancer patients remains poor. For those receiving radiation therapy, local control and survival have been shown to improve with increased doses; however, deliverable dose is often limited by associated toxicity. Therefore, methods that reduce dose to normal tissues and allow isotoxic escalation are desirable. Adaptive radiation therapy seeks to improve treatment by modifying the initial plan throughout delivery, and has been shown to decrease normal tissue dose. Studies to date suggest a trend of increasing benefit with increases in replanning frequency; however, replanning is costly in terms of workload and past studies implement at most weekly adaptation. The purpose of this thesis is to quantify the benefit associated with daily replanning and characterize the tradeoff between replanning frequency and adaptive benefit. A software tool is developed to facilitate planning studies and to introduce complimentary methods for evaluating adaptive treatments. Synthetic images and contours are xii generated for each fraction of a typical fractionation schedule using principal component analysis and a novel method of sampling coefficients that preserves temporal trends in the data (e.g. tumor regression). Using the synthetic datasets, a series of adaptive schedules ranging from no adaption to daily replanning are simulated and compared to quantify adaptive benefits and characterize tradeoffs with frequency. Daily replanning resulted in significant reductions in all normal tissue planning metrics when compared to no adaptation, and incremental reductions were observed with each increase in replanning frequency while the magnitude of average reductions decreased with each step. Modest correlation between absolute change in planning target volume over the course of treatment and reductions in both mean lung dose and mean esophageal dose were observed.
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Analyse de la contribution des kallicréines tissulaires 6 et 12 à la physiopathologie pulmonaire / Analysis of the contribution of tissue kallikreins 6 and 12 to lung pathophysiologyMichel, Noémie 26 March 2013 (has links)
Les kallicréines tissulaires humaines (KLK) ont récemment émergé comme une famille de protéases à serine pouvant jouer un rôle important dans la tumorigenèse. Le but de cette étude a été de mieux comprendre comment KLK6 et KLK12 pourraient intervenir dans la physiopathologie pulmonaire. Nous avons démontré qu’une expression ectopique de KLK6 induisait la prolifération des cellules A549 d’une manière dépendante de son activité enzymatique, une résistance à l’apoptose, ainsi qu’une translocation nucléaire de la β-caténine. Nous avons également montré une voie de signalisation impliquée dans la prolifération induite par KLK6 impliquant PAR2, EGFR et ERK. Nous avons identifié de nouveaux subtrats pour KLK12 : les CCN. Nous avons démontré que le clivage de CCN1 et CCN5 par KLK12 limitait leurs fixations avec le VEGF, BMP2 et le TGF-β1. / Recently, human tissue kallikreins (KLK) emerged as a new family of serine proteases which might play a major role in the tumorigenesis. The project aims at determining the contribution of KLK6 and 12 in lung pathophysiology. We showed that ectopic KLK6 promoted A549 cell proliferation in a protease activity-dependant manner, inhibited cell apoptosis and induced β-catenin nuclear translocation. Furthermore, this study uncovered a signaling pathway mediated by KLK6 in promoting A549 cell proliferation trough activation of the PAR2-EGFR-ERK pathway.We have also identified novel substrates of KLK12, the CCN family. We reported that KLK12-mediated proteolysis of CCN1 and CCN5 can reduce or abolish the binding of VEGF, BMP2, and TGF-β1.
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Molecular mechanisms of apoptosis in lung cancer: a role for retinoblastoma binding protein 6 (RBBP6) and its protein productsMotadi, Lesetja Raymond 24 August 2010 (has links)
RBBP6 (retinoblastoma binding protein 6) is a 250-kDa multifunctional protein that interacts
with both p53 and pRb and has been implicated in mRNA processing. It has also been
identified as an E3 ubiquitin ligase due to the presence of a RING finger domain and also
assumed to have a regulatory role of p53 due to the presence p53BD through MdM2,
although no substrate has been identified up to now. RBBP6 gene mutants are reported to be
resistant to apoptosis inducers, which led to a belief that mutation of this gene might result in
the development of lung cancer. Earlier localization and expression studies have shown that
RBBP6 expression and apoptosis levels are indirectly proportional. The purpose of this study
is to establish the expressional pattern of the RBBP6 gene in lung cancer at both mRNA and
protein levels. The objective is also to characterize the role of this gene and apoptosis in
diverse lung diseases. An understanding of the role of RBBP6 in the development of lung
diseases may lead to insights into developing new therapeutic measures for those lung
diseases in which apoptosis plays a prominent part. This thesis elucidate the possible role of RBBP6 in lung cancer and apoptosis, to establish
tissue distribution and expression levels of RBBP6 at protein and mRNA levels in lung
cancer by immunocytochemistry (ICC), in situ hybridization (ISH) and confirm findings by
quantitative RT-PCR. RBBP6 mRNA transcripts were expressed in the cytoplasm of normal
and tumour lung epithelium. In general, expression was highest in the cytoplasm of welldifferentiated
carcinoma and invasive carcinoma that showed signs of cells undergoing
mitosis. Immunolabelling results further showed high level of expression in all lung cancer
types except in Small and large cell carcinomas. The immunolabeling were confirmed by ISH
experiments and RT-PCR. In relation to p53, RBBP6 mRNA expression was higher in lung cancer cell lines that had
p53 silenced and apoptosis induced by TRAIL and camptothecin. There was no notable
change in the levels of p53 expression following RBBP6 silencing and apoptosis induction.
However, there was a little correlation between RBBP6 expression and apoptosis levels in
both lung cancer tissues by TUNEL and lung cancer cell line following apoptosis induction
by TRAIL. The ratio of Bax/Bcl-2 was seen to be upregulated following p53 and RBBP6
silencing after apoptosis induction. The most common mutation notable after RBBP6 DNA
sequencing was point mutations where only single nucleotide was mutated and mostly they
were observed in lung cancer tissues.
This was the first demonstration that RBBP6 is expressed in lung cancers. Because of the
ubiquitin-like nature of the protein and its localized up-regulation and corresponding proapoptotic
activity in lung cancer cells, it is possible that further characterization of this gene could lead to its manipulation as a diagnostic marker and a potential therapeutic target for
cancer treatment.
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The clinical care of patients with lung cancer : identifying and supporting those with unmet care needsBuchanan, Deans January 2010 (has links)
Lung cancer has developed from a rare condition into the leading cause of cancerrelated death in the United Kingdom. Lung cancer patients face a disease with a high symptom burden, increased psychosocial needs and a high mortality. Supportive care needs are often relevant from diagnosis. Despite this there are no clear follow-up structures for lung cancer patients that address both cancer management and supportive care. The aims of this study were to evaluate supportive care needs, assess predictors of such needs and identify factors which could aid service provision within Stobhill lung cancer services. Methods Supportive care needs were measured using an adapted Palliative Outcome Scale (POS), incorporated within a larger questionnaire. All lung cancer patients attending the clinic could complete this questionnaire. Respiratory symptoms, performance status, service usage, preferences and satisfaction were also assessed. Data were stratified to allow evaluation of three clinical groupings: all patients, newly diagnosed patients and patients in the last three months of life. Analyses were phased: descriptive analyses, univariate tests of association and multivariate regression. Results Three hundred and fifty three lung cancer patients completed questionnaires. The high symptom burden in lung cancer was confirmed. Anxiety, pain and dyspnoea were identified as the key issues. Poor performance status was identified to be an independent predictor of increased POS score, increased anxiety, increased pain and increased dyspnoea. There was no independent relationship between POS and survival. Although the majority of patients were satisfied with the care received, there was uncertainty regarding who was in charge of care and some disparity in preferred structure for follow-up. Conclusions Despite recent advances in lung cancer management, improvements are still required to address unmet supportive care needs of patients. Particular attention should be given to those with poorer performance status to effectively identify and meet such needs.
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Characterizing the impact of smoking and lung cancer on the airway transcriptome using RNA sequencingVick, Jessica Lynn January 2012 (has links)
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. / Cigarette smoke creates a molecular field of injury in epithelial cells that line the respiratory tract. We hypothesized that transcriptome sequencing (RNA-seq) will enhance our understanding of the field of molecular injury in response to tobacco smoke exposure and lung cancer pathogenesis by identifying gene expression differences not interrogated or accurately measured by microarrays. We sequenced the high- molecular weight fraction of total RNA (>200 nt) from pooled bronchial airway epithelial cell brushings (n = 3 patients per pool) obtained during bronchoscopy from healthy never smoker (NS) and current smoker (S) volunteers and smokers with (C) and without ( C) lung cancer undergoing lung nodule resection surgery. RNA-seq libraries were prepared using two distinct approaches, one capable of capturing non-polyadenylated RNA (the prototype NuGEN Ovation RNA-seq protocol) and the other designed to measure only polyadenylated RNA (the standard Illumina mRNA-seq protocol) followed by sequencing generating approximately 29 million 36 nt reads per pool and approximately 22 million 75 nt paired-end reads per pool, respectively. The NuGEN protocol captured additional transcripts not detected by the Illumina protocol at the expense of reduced coverage of polyadenylated transcripts, while longer read lengths and a paired-end sequencing strategy significantly improved the number of reads that could be aligned to the genome. The aligned reads derived from the two complementary protocols were used to define the compendium of genes expressed in the airway epithelium (n = 20,573 genes). Pathways related to the metabolism of xenobiotics by cytochrome P450, retinol metabolism, and oxidoreductase activity were enriched among genes differentially expressed in smokers, whereas chemokine signaling pathways, cytokine-cytokine receptor interactions, and cell adhesion molecules were enriched among genes differentially expressed in smokers with lung cancer. There was a significant correlation between the RNA-seq gene expression data and Affymetrix microarray data generated from the same samples (P < 0.001); however, the RNA-seq data detected additional smoking- and cancer-related transcripts whose expression was were either not interrogated by or was not found to be significantly altered when using microarrays, including smoking- related changes in the inflammatory genes SIOOA8 and SIOOA9 and cancer-related changes in MUC5AC and secretoglobin (SCGB3Al). Quantitative realtime PCR confirmed differential expression of select genes and non-coding RNAs within individual samples. These results demonstrate that transcriptome sequencing has the potential to provide new insights into the biology of the airway field of injury associated with smoking and lung cancer. The measurement of both coding and non-coding transcripts by RNA-seq has the potential to help elucidate mechanisms of response to tobacco smoke and to identify additional biomarkers of lung cancer risk and novel targets for chemoprevention. / 2031-01-01
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Promotion Of Lung Cancer By Interleukin-17Unknown Date (has links)
No description available.
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Promotion Of Lung Cancer By Interleukin-17Unknown Date (has links)
No description available.
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Promotion Of Lung Cancer By Interleukin-17Unknown Date (has links)
No description available.
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The Effect of Polydimethylsiloxane Substrate Modification on A549 Human Epithelial Lung Cancer Cell Morphology and BiomechanicsWard, Sherissa A. 01 May 2015 (has links)
In this thesis the effect of mechanical stimuli on A549 lung cancer cells is studied. Modifications of polydimethylsiloxane (PDMS) surfaces are employed to alter the mechanical stimuli applied to the cells. Flat substrates are first studied and then micropillared substrates are designed, fabricated, and tested as a method to alter the mechanical properties of the PDMS surfaces.
Molds with micro-pillars are designed then fabricated from silicon using deep reactive ion etching. From these molds, a negative then a positive replicate is made using PDMS. The pillared PDMS substrates are fabricated in 10 geometries and used for experiments. A549 cells are cultured on these surfaces then analyzed using fluorescence microscopy and atomic force microscopy (AFM). Fluorescence microscopy images processed by ImageJ software measure the cell spreading area (m2) while AFM quantifies the cell stiffness (kPa).
For flat substrates, the cell stiffness and spreading area increase with increasing substrate stiffness. Further, results on pillared substrates show a similar trend based on pillar geometry changes. For pillared substrates, the A549 cell stiffness and spreading area increase as the height decreases, yet there is decreased cell stiffness and spreading area as the diameter and spacing decreases. The experiments show that changes in surface properties and only mechanical stimuli alter cellular morphology and biomechanics
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