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.

Syftet med denna systematiska litteraturstudie är att undersöka upplevelser hos anhörigvårdare till lungcancerpatienter. Artikelsökningar har skett i Cinahl och Pubmed. Tiden för anhörigvårdaren kan se olika ut, kort och intensiv eller lång och utmattande. Upplevelser så som skräck är vanligt förekommande direkt efter lungcancerdiagnosen både för patient och vårdare. Detta för att de anhöriga ställs inför ett klart hot om en kommande förlust samt skrämmande tankar kring döden. Hälsan försämras för anhörigvårdaren under vårdtiden och vissa drabbas av depression. De social relationerna försämras, vissa upphör helt då anhörigvårdaren får en känsla av att de alltid måste vara tillgängliga för den sjuke. Vårdbördan kan vara tung och emotionellt stöd kan vara nödvändigt. Trots det väljer många att inte ta emot eller söka något stöd.Inte bara hälsan förändras under sjukdomstiden utan också mycket annat, den som tidigare haft en passiv roll i hushållet kan bli tvungen att ta en mer aktiv roll i skötseln av hem och ekonomi. Trots att anhörigvårdare ofta känner sig utanför och övergivna väljer de att inte uttrycka sina känslor när de blir tillfrågade eftersom det finns en rädsla att ta fokus från patienten.

Bakgrund: Lungcancer är den femte vanligaste cancerformen i Sverige, med dålig prognos och leder ofta till döden. Då bot inte längre är möjligt blir palliativ vård aktuellt. Detta betyder att patienten bör vara fri från smärta och plågsamma symtom, att man varken påskyndar eller skjuter upp döden och att döendet ska ses som en normal process. Syfte: Syftet var att beskriva patienters upplevelser av att leva med lungcancer i den palliativa fasen. Metod: Studien genomfördes som en litteraturstudie (overview), baserad på empiriska studier inom det valda ämnet. Sökning skedde i databaserna Cinahl, PubMed och PsycInfo.  Litteraturstudien grundades på tolv kritiskt granskade studier, både kvalitativa och kvantitativa, publicerade i vetenskapliga tidskrifter. Resultat: I resultatet framkom fysiska, psykiska, existentiella och sociala upplevelser. Resultatet presenterades med inspiration av Peter Strangs modell om symtomkontrollens betydelse i den palliativa vården. Diskussion: Resultatet diskuterades utifrån två fynd. Ett fynd var dyspné som upplevdes smärtsamt och förknippades med ångest och oro. Det andra fyndet var upplevelsen av förlust av olika slag. Slutsats: Svårt sjuka och döende patienter har rätt att bli vårdade av omsorgsfulla, medkännande och kunniga människor, som försöker förstå deras behov och som upplever det givande att hjälpa dem möta döden. / Background: Lung cancer is the fifth most common form of cancer in Sweden, with a poor prognosis and it often leads to death. As there is no cure, palliative care is applied. This means that the patient should not have to suffer from pain and agonizing symptoms. There is no affect that either hastens or postpones death and death should be considered as a normal process. Purpose: The purpose was to describe patients' experiences with regard to living with lung cancer in the palliative stage. Method: The study was performed as a literature overview, based on empirical studies within the chosen subject. Research was done using Cinahl, PubMed and PsycInfo databases. The literature study was based on twelve critically reviewed studies, qualitative and quantitative, published in scientific magazines. Results: Physical, mental, existential and social experiences emerged from the results. Results are presented, inspired by Peter Strang's model about the meaning of using system control in palliative care was used in the presentation of the results. Discussion: The result was based on two elements. A finding was dyspnea and was experienced painful and was associated with anxiety and worry. The second finding was the experience of loss of various kinds.   Conclusion: Patients who are fatally ill and facing death have the right to be nursed in a caring, empathetic way by experienced people who understand their needs and can appreciate the rewarding to meet death.

Bakgrund: Ivärlden dör ca 1,4 miljoner människor av lungcancer varje år. Prognosen förlungcancer är sämre än vid insjuknande i andra cancerformer. Mer än fem årsöverlevnad är ovanlig bland både kvinnor och män. Kunskapom erfarenheter av lungcancer är viktiga eftersom det kan leda till bättrevårdupplevelse för patienten. Syfte: Attbeskriva personers erfarenheter av att leva med lungcancer. Metod:Studien genomfördes som en litteraturstudie där vetenskapliga studier söktesgenom databassökning samt manuell sökning. Tolv vetenskapliga studier analyserades.Resultat: Resultatet baseras på fysiska-, psykiska- och socialaerfarenheter. Det framkom att fysisk- och mental trötthet, smärta,andningssvårigheter, rädsla, hopp, ångest och oro, förlust av relationer samtskuldkänslor är erfarenheter som personer med lungcancer har. Slutsats/konklusion:God kommunikation/informationmellan sjuksköterska och patient är viktigt. Medvetenhet omerfarenheter av lungcancer kan leda till attlivskvalitén höjs och att vårdupplevelsen förbättras. / Background: In the world around 1.4 million people are dying from lung cancer each year. The prognosis is worse than for other diagnosis. More than five year survival is rare among both women and men. Awareness of experiences of lung cancer is important and it can lead to a better experience for the patient. Aim: To describe people's experiences of living with lung cancer. Method: The study was a literature review and scientific studies were found in databases and in manual searches. Twelve scientific studies were analyzed. Results: The results are based on physical, psychological and social experiences. The findings resulted in nine themes: physical- and mental fatigue, pain, breathing difficulties, fear, hope, worry and anxiety, loss of relationships and feelings of guilt. These are experiences that people with lung cancer have. Conclusion: Good communication/ information between the nurse and patient are important. Awareness of the experiences of lung cancer may improve patients' quality of life and experiences of care.

Bakgrund: 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. Syftet: Att beskriva faktorer som påverkar hur patienter med lungcancer upplever sin smärta och mötet med sjuksköterskan. Metod: En systematisk litteraturstudie genomfördes där både kvalitativa och kvantitativa artiklar granskades. Resultat: 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. Diskussion: 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. / Background: 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. Purpose: To describe the factors that affect how patients with lung cancer experience their pain and the contact with the nurse. Method:  A systematic literature study was conducted in which both qualitative and quantitative articles were reviewed. Conclusion: 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. Discussion: 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.

In 2004, lung cancer has been the leading cause of cancer death in Taiwan. Many studies demonstrate that vitamin A plays a crucial role in the prevention of lung cancer. However, few epidemiologic studies have examined the association of dietary vitamin A/precursors and lung cancer in Taiwan. Therefore, a case-control study was conducted to investigate the relationship between the consumption of local common foods that are rich in vitamin A/precursors and the risk of lung cancer. The cases were 301 newly diagnosed patients with histopathologically confirmed primary lung cancer. Two control groups were recruited: 602 hospital controls and 602 neighborhood controls. The consumption of 13 food items and vitamin supplements was estimated with the use of a structured food-frequency questionnaire in face-to-face interviews. Adjusted odds ratios (AOR) and the corresponding 95% confidence intervals (CI) were evaluated with controlling for potential confounders, using the conditional logistic regression model. It was found that reduced risk for lung cancer was associated with increased intakes of vitamin A, a-carotene, or b-carotene from various food groups except fruits. However, inverse associations were not observed for vitamin A, a-carotene, or b-carotene intake from various food items, except garland chrysanthemum and sweet potato leaves. On the other hand, retinol intake from food groups or items was not correlated with lung cancer development. Additionally, more servings of vegetables (AOR for the highest versus the lowest quartile = 0.67-0.70, 95% CI = 0.42-1.08, plinear trend = 0.04), garland chrysanthemum (AOR for the highest versus the lowest tertile = 0.58-0.74, 95% CI = 0.37-1.14, plinear trend = 0.01-0.04) and sweet potato leaves (AOR for the highest versus the lowest tertile = 0.43-0.65, 95% CI = 0.28-0.96, plinear trend £ 0.03) were associated with the reduced risk for lung cancer. In conclusion, there were protective effects of dietary intake of vitamin A, a-carotene and b-carotene. The vegetables provided higher potential protection against development of lung cancer than the fruits, especially for garland chrysanthemum and sweet potato leaves. Therefore, our findings suggest that more consumption of garland chrysanthemum and sweet potato leaves might reduce the risk of lung cancer in Taiwan.

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.

There is evidence of a relationship between pain and associated symptoms, specifically constipation and dyspnea, and quality of life. Literature supports that endstage lung cancer patients suffer more symptoms than those with other types of cancers, and the course of treatment is primarily palliative, as many of these diagnosed patients cannot be cured. The purpose of this secondary analysis of data was to evaluate the relationships between pain and other common symptoms in end stage lung cancer patients in hospice care, and the relationships among pain, dyspnea, constipation and quality of life. The study sample included fifty lung cancer patients admitted to a hospice program, reporting pain. A series of Pearson’s correlations were used to analyze relationships between the variables pain intensity, pain distress, dyspnea intensity, dyspnea distress, constipation intensity and the relationships of these variables with quality of life. The results showed positive significant correlations between pain intensity and pain distress (r = .44, p = .002), dyspnea intensity and dyspnea distress (r = .47, p = .001), and constipation intensity and quality of life (r = -.57, p = .013). Pain and the relief of pain have been studied extensively in cancer patients, yet little research has been done in the way of side effects of opioid use, specifically constipation. This study reinforces to vi nursing the importance of a thorough assessment upon admission to hospice, and at each subsequent nursing visit, which includes a bowel habit history, current medications in use, potential risk for developing constipation and management of constipation once it is present. Hospice patients with lung cancer are reporting a decrease in quality of life secondary to constipation. Prevention or rapid alleviation of this symptom will provide comfort and allow the patient to focus on important end of life tasks.

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses. A central focus of immunotherapy is to develop vaccine adjuvants that are capable of enhancing a protective adaptive immune response. Microbial adjuvants in vaccines activate key transcription factors, including NF-κB and interferon response factors (IRF). The individual role of these transcription factors in successful vaccines is not clear. We used constitutively active IKKΒ (CA-IKKΒ) expressed in an adenoviral vector (AdIKK) to determine the role of classical NF-κB activation in a vaccine-induced immune response. In an in vivo model, AdIKK induced rapid and sustained NF-κB-driven inflammation in the lungs compared to the control virus. AdIKK infection had no impact on the magnitude of T cell activation as measured by IFN-γ production; however pulmonary inflammation resulted in increased cellularity of draining lymph nodes (LN) at early timepoints resulting in increased early antibody and T cell responses. Taken together, these findings show that IKKΒ-induced NF-κB activation of an inflammatory response affects the kinetics, but not the magnitude of the adaptive immune response. NF-κB is activated in many tumor types and contributes to the progression of cancer by suppressing apoptosis, and enhancing proliferation, angiogenesis and metastasis. NF-κB is also activated in other cells within the tumor microenvironment and promotes inflammation initiated by neutrophils and macrophages. In addition to inflammatory cells, T cells can be found within the tumor microenvironment and are associated with improved patient survival. Using CA-IKKΒ, we sought to determine if NF-κB activation in tumor cells could promote T cell mediated tumor immunity. In both primary tumors and a metastatic tumor model, we found that NF-κB expression in tumors rendered immunogenic through expression of Kb-OVA led to tumor rejection or growth suppression. Tumor regression was mediated by increased CD8 T cell recruitment by chemokines. Microarray results showed increases in T cell chemokines, including CCL2 and CCL5. Knock-down of CCL2 by Lentiviral shRNA in LLC-OVA-IKK cells resulted in abrogation of tumor regression. These results suggest that NF-κB is capable of promoting immune surveillance in tumors through increased recruitment of T cells. Overall, my dissertation highlights beneficial roles of IKKΒ-induced activation of NF-κB in two separate systems: vaccine induced immune responses and tumor immune surveillance.

Abstract Although the critical role of the small GTPases Ras and Ral in oncogenesis has been well documented, much remains to be investigated about the molecular mechanism by which these GTPases regulate malignant transformation. The work under this thesis made two major contributions to this field. The first is the discovery that K-Ras, RalA and/or RalB are required for the maintenance of the high levels of the anti-apoptotic protein survivin in some human cancer cells, and the second is the demonstration that down regulation of K-Ras, RalA and/or RalB, but not Raf-1 or Akt1/2, stabilizes the tumor suppressor p53 and reactivates it to inhibit malignant transformation in human cancer cells with mutant K-Ras and wild type p53. Here we found that depletion of K-Ras leads to decreased survivin levels in human cancer cells that harbor mutant K-Ras but not those with wild type Ras. The mechanism by which this occurs involves ubiquitination and subsequent proteasome-mediated degradation of survivin. The presence of mutant K-Ras alone was not sufficient to predict the effects of RalA/B depletion on survivin levels. Indeed, depletion of RalA and/or RalB reduces survivin levels in human cancer cells with wild type p53 and mutant K-Ras, but not in those with mutant p53 and/or wild type K-Ras. The functional relevance of these findings to malignant transformation was further supported by the demonstration that compromising the expression of survivin by siRNA leads to reduction of mutant K-Ras-driven invasion and anchorage-independent growth. Furthermore, in this thesis, we have discovered that down regulation of K-Ras, RalA and/or RalB using siRNA leads to increased levels of functional p53 that is capable of regulating its target genes. The mechanism by which depleting K-Ras, RalA and RalB increases the levels of p53 involves an increase in the half-life of the p53 protein concurrent with an increase in the phosphorylation of serine-15 of p53, a marker of p53 stability. Finally, we demonstrated that depletion of K-Ras, RalA and/or RalB interferes with cell cycle progression, anchorage-independent growth and invasion in a p53-dependent manner. In summary, the studies suggest that mutant K-Ras contributes to the maintenance of the aberrantly-high survivin levels by regulating its stability, and that the ability of mutant K-Ras to induce malignant transformation is, at least in part, dependent of these high levels of survivin. The work of this thesis also suggests that the expression of K-Ras, RalA and/or RalB proteins is critical to maintain low levels of p53, and that down regulation of these GTPases reactivates p53 by significantly enhancing its stability, and this contributes to suppression of malignant transformation.