<p><strong>Bakgrund:</strong> Lungcancer är den femte vanligaste cancerformen och den cancerrelaterade dödsorsaken i Sverige. De flesta patienter som insjuknar i lungcancer är runt 70 år, knappt ett hundratal personer varje år insjuknar före 50-årsåldern. <strong>Syftet:</strong> Att beskriva faktorer som påverkar hur patienter med lungcancer upplever sin smärta och mötet med sjuksköterskan. <strong>Metod:</strong> En systematisk litteraturstudie genomfördes där både kvalitativa och kvantitativa artiklar granskades. <strong>Resultat:</strong> I resultatet visade att smärtupplevelsen och mötet med sjuksköterskan är individuell och beror på många olika faktorer. Den fysiska och psykiska smärtan hörde ihop och påverkade varandra . Patienterna upplevde att sjuksköterskornas tidsbrist kunde skapa missförstånd, att de fick bristfällig information och att deras smärta kunde underskattas. <strong>Diskussion:</strong> Resultatet diskuterades utifrån Travelbees omvårdnadsteori. Sjuksköterskan bör se patienten som en individ och bemöta patientens smärta med respekt, ge honom den tid, den förståelse och den information han behöver.</p> / <p><strong>Background</strong>: Lung cancer is the fifth most common form of cancer and a cancer-related cause of death in Sweden. The majority of patients suffering from lung cancer are around 70 years old, barely a hundred people each year become ill before the age of 50 years. <strong>Purpose</strong>:<strong> </strong>To describe the factors that affect how patients with<strong> </strong>lung cancer experience their pain and the contact with the nurse. <strong>Method</strong>:  A systematic literature study was conducted in which both qualitative and quantitative articles were reviewed. <strong>Conclusion</strong>: The result showed that pain perception and the meeting with the nurse is individual and depends on many factors. The physical and mental pain went together and influenced each other. Patients felt that nurses' lack of time, could create misunderstandings, meaning that they could receive inadequate information and that their pain could be underestimated. <strong>Discussion</strong>: The results were discussed based on Travelbees nursing theory. The nurse should see the patient as an individual and treat his pain with respect, giving him the time, the understanding and the information he needs.</p>

<p>This thesis investigated the predictive and the prognostic powers of angiogenesis related markers in both operable and inoperable non-small cell lung cancer (NSCLC) patients.</p><p>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. </p><p>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.</p><p>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.</p><p>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. </p><p>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. </p><p> 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. </p>

Aldehydes in lung cancer cell culture have been investigated using gas chromatography/mass spectrometry and solid-phase microextraction with on-fiber derivatization. In this study, the poly(dimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used and o-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA) was first loaded on the fiber. Aldehydes in the headspace of lung cancer cell culture were extracted by solid-phase microextraction (SPME) fiber and subsequently derivatized by PFBHA on the fiber. Finally, the aldehyde oximes formed on the fiber were analyzed by gas chromatography/mass spectrometry (GC/MS). Using this method, acetaldehyde decrease was found in both non-small lung cancer cell cultures studied compared to the medium control study. The results of spiking the cell culture with acetaldehyde solution showed that 5 million SK-MES-1 cell lines could consume up to 4.5 uM acetaldehyde in 15-ml medium, and 5 million NCI-H522 cell lines could consume 5.9 uM acetaldehyde in 15-ml medium. The decrease of acetaldehyde may contribute to the metabolism of lung cancer cells. It was proved that GC/MS and SPME with on-fiber derivatization is a simple, rapid, sensitive and solvent-free method for the detection of aldehydes in lung cancer cell culture.

This 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.

The goal of this thesis is to analyze and understand the risks of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer with respect to the provinces of Turkey according to the results of spatial analysis. The insurance sector of the country needs that kind of analysis to make more precise pricing in insurance products. Especially in health and life insurance products, morbidities like COPD and lung cancer may aect the life expectancy as much as the premiums. COPD and lung cancer prevalence may exhibit spatial autocorrelation due to spatial similarity of provinces. Hence understanding of spatial pattern of COPD and lung cancer prevalence may provide better actuarial decisions. In this research, common risk factors of COPD and lung cancer are considered to be tobacco sales, air pollution, urbanization, gross schooling rate, life expectancy, median age and GDP per capita of the provinces. The spatial patterns of these factors in Turkey as well as their correlations to COPD and lung cancer prevalence are explored in this study. The raw data of the morbidities (COPD and lung cancer) are collected from the Social Seiv curity Institution (SGK) and the useful data are selected in these raw data. The data of the independent variables are collected and derived from the Turkish Statistical Institute (TUIK) and Tobacco and Alcohol Market Regulatory Authority (TAPDK). First of all, COPD prevalence ratios and lung cancer prevalence ratios are grouped by 81 provinces of Turkey and every morbidity is separated by gender. Then, it needs to be decided the variables which define prevalence of COPD and that of lung cancer. Age, gender, socio-economic status, urbanization, schooling rate, life expectancy, tobacco sales and air quality may be some of the random variables which are categorized by provinces for both morbidities. After data collection spatial analysis is applied with visualization, explanatory analysis and modeling by using Geographic Information Systems (GIS). In visualization, general spatial patterns are identified for morbidities and variables. In explanatory analysis part, proximity matrices are used to evaluate Moran&rsquo / s I values for understanding the spatial autocorrelation. Then, these Moran&rsquo / s I values are used for plotting correlograms in order to follow the spatial dependence better. After identifying spatial dependence of the variables, Ordinary Linear Regression and Spatial Regression models are established and compared. Finally, as a result of those findings in the analysis, actuarial risk assessments are found for both two morbidities with respect to provinces and gender. The risk assessments are mapped and compared with the explanatory variables in the models which are found in the previous part and the relations between risks and variables are observed. As a result, the parameters show spatial autocorrelation which means that / financial risk assessments of COPD and lung cancer should be taken into account when deciding the pricing of some actuarial products such as health insurance. Generally, spatial correlation is ignored in this kind of calculations, but due to the high autocorrelation the results may indicate serious change. From the actuarial perspective, the results of the analysis are suggested to be used in health insurance premium pricing. Since the analysis could not have been made on the basis of individuals, and financial burden of morbidities for insurance companies are not given clearly, it is not possible to calculate any health insurance product premium, but it is more appropriate to consider the importance of these risk results in the calculations of health insurance products.

Arsenic is a well-known lung carcinogen in humans. In 2006, IARC upgraded inorganic lead as a possible human carcinogen (2A). The aim of this thesis has been to evaluate the lung cancer mortality and incidence in long-term exposed primary lead smelter workers and also to estimate present exposures to arsenic and lead in relation to those occurring in the past. The basic cohort (N=3832 workers; hired before 1967 and followed up from 1950-1981; SMR comparisons with general and local reference populations) showed an excess of deaths for total mortality, malignant neoplasms (e.g. lung and stomach cancer), ischaemic heart diseases, and cerebrovascular diseases compared to the general population. In a subcohort of lead workers (N=437; regular blood lead sampling since 1950) only the raised SMR for lung cancer (162) was sustained. In a follow-up study of the basic cohort (N=3979), a subcohort of lead exposed workers (N=1992) was formed. The expected mortality in 1955-1987 and cancer incidence in 1958-1987 were calculated relative to county rates. A cumulative blood lead index (CBLI) was used for dose-response analyses. The lung cancer incidence was raised in the total cohort (SIR 2.8; 95 % CI 2.1 3.8). A higher lung cancer risk was observed in workers hired before 1950 (SIR 3.6; 95 % CI 2.6-5.0). The increased lung cancer risks were further elevated in the subcohort of lead exposed workers, especially in the highest exposed subgroup (SIR 5.1; 95 % 2.0-10.5; latency period of 15 y). No excesses of other malignancies were observed. The increased relative risks for lung cancer may have been caused by interactions between inorganic lead and other substances at the smelter, e.g. arsenic. To further analyze the effects from inorganic lead, two subcohorts of workers at the lead departments were formed from the original cohort (N=3979), one of 710 workers and the other of 383 workers. The lung cancer incidence was raised in both subcohorts (Lead subcohort 1; SIR 2.4; 95 % CI 1.2-4.5; Lead subcohort 2; SIR 3.6; 95 % CI 1.2-8.3). Among the 10 workers that had developed lung cancer in lead subcohort 1 all but one had a considerable exposure also to arsenic. Thus, a possible interaction effect between lead and arsenic may explain the increased lung cancer risks. To further elucidate the impact from lead and arsenic a case control study was undertaken. In the basic cohort (N=3979), 46 male workers had contracted respiratory malignancies. They were compared with 141 agematched male referents from the primary smelter by conditional logistic regression analysis using smoking habits, cumulative blood lead and air arsenic exposure as predictor variables. The lung cancer cases showed a significantly higher smoking rate than referents (Odds ratio, OR = 4.0; 95 % CI 1.6-10.1; p=0.003). When restricted to smokers, the cumulative arsenic air exposure index, but not the lead exposure indices, were significantly higher among the cases (OR=1.07; 95 % CI 1.02-1.11; p = 0.005). Accordingly, cumulative arsenic exposure and smoking were identified as significant risk factors for the development of lung cancer in the final analyses, while lead exposure was not a significant risk factor. However, inorganic lead still may play a minor role in the multifactorial genesis of lung cancer. These studies describe risks from exposures occurring from time periods before 1950 up to 1981. Because of the long latency period for lung cancer, exposures after 1970 probably have had limited impact on the reported results. Compared to the levels in the early 1970´s present exposures to arsenic are lower by a factor of ten or more and risks probably correspondingly lower.

Proteins are essential building blocks in every living cell, and since the complete human genome was sequenced in 2004, researchers have attempted to map the human proteome, which is the functional representation of the genome. One such initiative is the Human Protein Atlas programme (HPA), which generates monospecific antibodies towards all human proteins and uses these for high-throughput tissue profiling on tissue microarrays (TMAs). The results are publically available at the website www.proteinatlas.org. In this thesis, TMAs were used for analysis of expression patterns in various research areas. Different search queries in the HPA were tested and evaluated, and a number of potential biomarkers were identified, e.g. proteins exclusively expressed in islets of Langerhans, but not in exocrine glandular cells or other abdominal organs close to pancreas. The identified candidates were further analyzed on TMAs with pancreatic tissues from normal and diabetic individuals, and colocalization studies with insulin and glucagon revealed that several of the investigated proteins (DGCR2, GBF1, GPR44 and SerpinB10) appeared to be beta cell specific. Moreover, a set of proteins differentially expressed in lung cancer stroma was further analyzed on a clinical lung cancer cohort in the TMA format, and one protein (CD99) was significantly associated with survival. In addition, TMAs with tissue samples from different species were generated, e.g. for mapping of influenza virus attachment in various human and avian tissues. The results showed that the gull influenza virus H16N3 attached to human respiratory tract and eye, suggesting possible transmission of the virus between gull and human. TMAs were also used for analysis of protein expression differences between humans and other primates, and two proteins (TCF3 and SATB2) proved to be significantly differentially expressed on the human lineage at both the protein level and the RNA level.   In conclusion, this thesis exemplifies the potential of the TMA technology, which can be used for analysis of expression patterns in a large variety of research fields, such as biomarker discovery, influenza virus research or further understanding of human evolution.

Purpose. Low-dose computed tomography is an important imaging modality for screening and surveillance of lung cancer. The goal of this study was to determine the extent to which dose could be minimized while maintaining diagnostic accuracy through knowledgeable selection of reconstruction techniques. Methods. An anthropomorphic phantom was imaged on a 320-slice volumetric CT scanner. Detectability of small solid lung nodules was evaluated as a function of dose, patient size, reconstruction filter and slice thickness by means of 9-alternative forced-choice observer tests. Results. Nodule detectability decreased sharply below a threshold dose level due to increased image noise. For large body habitus, optimal (smooth) filter selection reduced dose by a factor of ~3. Nodule detectability decreased for slice thicknesses larger than the nodule diameter. Conclusions. Radiation dose can be reduced well below current clinical protocols. Smooth reconstruction filters and avoidance of large slice thickness permits lower-dose techniques without tradeoff in diagnostic performance.

Non-Small-Cell-Lung Cancer (NSCLC) patients with mutations in EGFR have greater response rates and survival when treated with the tyrosine kinase inhibitor erlotinib. To elucidate how erlotinib inhibits EGFR, this study included: 1) inhibiting an EGFR mutant cell line to reveal EGFR regulated phosphotyrosine (pY) sites; 2) comparing erlotinib sensitive and insensitive cell lines to reveal functionally important pY sites; 3) revealing novel pY sites. Observations were collected using the LTQ-Orbitrap mass spectrometer. This study identified five new EGFR regulated pY sites and five pY sites that correlated with erlotinib sensitivity; the majority of them are related to cell-cell interactions. By comparing all observed pY sites to the Phosphosite and PhosphoELM database, our results included 67 unregistered sites. This study has identified novel biomarkers and potential therapeutic targets, many of which were associated with cell migration and adhesion function. Further functional validation is necessary.

Non-Small-Cell-Lung Cancer (NSCLC) patients with mutations in EGFR have greater response rates and survival when treated with the tyrosine kinase inhibitor erlotinib. To elucidate how erlotinib inhibits EGFR, this study included: 1) inhibiting an EGFR mutant cell line to reveal EGFR regulated phosphotyrosine (pY) sites; 2) comparing erlotinib sensitive and insensitive cell lines to reveal functionally important pY sites; 3) revealing novel pY sites. Observations were collected using the LTQ-Orbitrap mass spectrometer. This study identified five new EGFR regulated pY sites and five pY sites that correlated with erlotinib sensitivity; the majority of them are related to cell-cell interactions. By comparing all observed pY sites to the Phosphosite and PhosphoELM database, our results included 67 unregistered sites. This study has identified novel biomarkers and potential therapeutic targets, many of which were associated with cell migration and adhesion function. Further functional validation is necessary.