Bakgrund: Cancerfallen i Sverige har fördubblats sedan 1970-talet och om cirka 20 år uppskattas 100 000 nya personer insjukna i cancer per år. Att drabbas av cancer anses vara en av de mest stressfyllda situationer en person kan uppleva och sjukdomen påverkar patienten både fysiskt, psykiskt och existentiellt. För att lättare hantera sin nya vardag kan patienten behöva tillämpa olika copingstrategier som används för att hantera svåra påfrestningar.  Syfte: Syftet med studien var att utifrån ett patientperspektiv beskriva copingstrategier som kan hjälpa patienter med avancerad cancer.  Metod: En litteraturstudie med 14 kvalitativa vetenskapliga artiklar genomfördes. Artiklarna analyserades utifrån Lundman och Hällgren-Graneheims (2017) manifesta innehållsanalys.  Resultat: Resultatet delades in i fyra kategorier och tretton underkategorier. Kategorierna som framkom var; Viljan att styra över sitt liv, uppmuntrande känslor, socialt stöd samt andligt stöd. Slutsats: Sjuksköterskan behöver agera på ett sådant sätt att patientens hälsa ökar och lidandet minskar. Sjuksköterskan behöver också utgå ifrån patientens unika och subjektiva livsvärld eftersom det är först då som patientens copingstrategier kan identifieras och stärkas. Tillgodosedda copingstrategier leder till att patientens vardag och liv kan genomsyras av en känsla av hanterbarhet, begriplighet och meningsfullhet.

<p>Cancer upplevs ofta som en hotfull och farlig sjukdom. Många människor som har haft cancer drabbas även senare i livet av ett återinsjuknande. Vårdpersonals kunskap om upplevelser av att drabbas av ett återinsjuknande är otillräckliga, vilket leder till att människor i dessa situationer inte får adekvat stöd och hjälp. Syftet med examensarbetet var att belysa människors upplevelser av att återinsjukna i cancer. Fyra stycken självbiografier analyserades utifrån en kvalitativ manifest innehållsanalys med en induktiv ansats. Analysen resulterade i tre kategorier: viljan att leva, upplevelsen av lidande och upplevelsen av att vilja ge upp. Huvudfynden som framträdde var att de upplevde en rädsla inför döden, en själslig smärta och en upplevelse av kaos, vilka uttrycktes genom en upplevelse av lidande. Hopplöshet, oförståelse och förtvivlan var även framträdande upplevelser. En del upplevelser genomsyrades av en stark livsvilja, livskraft och en positiv inställning vilket visade att de ville fortsätta kämpa för att överleva. Det är betydelsefullt att sjuksköterskor tar de som återinsjuknat på största allvar för att de inte ska behöva lida i det tysta. Dessa människor måste uppmärksammas mer och omvårdnaden måste förbättras så att deras behov tillfredställs och att deras livskvalitet stärks.</p> / <p>Cancer is often perceived as a threatful and dangerous disease. A lot of people with a history of cancer also suffer a relapse later in their life. Nursing staff’s knowledge of experiences of being affected by a relapse is insufficient, resulting in that people in these situations do not receive adequate support and assistance. The aim of this Bachelor thesis was to illuminate people’s experiences of a cancer relapse. Four autobiographies were analyzed from a qualitative manifest content analysis with an inductive approach. The analysis resulted in three categories: the will to live, the experience of suffering and the experience of the desire to give up. The main findings were that they experienced a fear of death, a mental pain and an experience of chaos, which were expressed through an experience of suffering. Hopelessness, incomprehension and despair were also prominent experiences. A number of experiences were permeated by a strong will to live, vitality and a positive attitude which showed that they wanted to continue the struggle to survive. It is important that nurses take patients who relapse seriously, because these patients should not have to suffer in silence. These people require more attention and the nursing care must be improved so their needs are satisfied and the quality of life is strengthened.</p>

<p><p>Syftet med litteraturstudien var att genom litteraturen redogöra för cancersjuka ungdomars livskvalitet och hur de hanterar sin sjukdom. Denna studie är en beskrivande litteraturstudie där författarna sökte vetenskapliga artiklar på Medline, Cinahl, SweMed+ och PsykInfo. I resultatet redovisas femton artiklar. Resultatet visade att socialt stöd i form av föräldrar och en speciell vän visade ha stor betydelse för ungdomarnas välmående. Ungdomarna beskrev också att det kändes bra att prata med andra ungdomar i samma situation. Att ha en positiv inställning och humor hjälpte ungdomarna att hantera sin sjukdom. Ett sätt att komma ifrån sjukdomen, och slippa tänka på den för ett tag var att försöka känna sig normal. Detta gjorde de till exempel genom att bära accessoarer, moderna kläder och testa sina gränser. I och med att ungdomarna spenderade så mycket tid på sjukhus blev de isolerade, vilket skapade en utanförkänsla gentemot friska ungdomar. Förändrat utseende, rädsla och utanförskapskänsla är faktorer som påverkade ungdomars livskvalitet negativt. Det visade sig att de cancersjuka ungdomarna hade lägre livskvalitet än friska ungdomar, men desto längre tid det gick efter diagnosen desto högre blev deras livskvalitet. Flickor visade sig generellt ha bättre välbefinnande än pojkar.</p></p> / <p>The aim of this literature study was to investigate how adolescents with cancer cope with there disease and how it effect their quality of life (QoL). This study was a descriptive literature study were the authors searched for scientific articles in the databases Medline, Cinahl, SweMed+ and PsykInfo. The result is based on fifteen articles. The result showed that social support such as parents and a special friend is important for the adolescents' well-being. The adolescents also described that it felt god to have someone to talk to that was in the same situation. A positive attitude and humour helped the adolescents to cope with their disease. One way to escape from the disease was trying to feel normal, a way of doing that was to wear accessories, modern clothes and pushing their limits. The adolescents spent a lot of time in the hospitals thus made them isolated, which resulted in alienation. Changed body image, fear and alienation are all factors that influence on the adolescents QoL. It was showed that adolescents with cancer had lower QoL than healthy adolescents, but as time pass by their QoL increased. In general the girls hade better QoL than the boys.</p>

<p><strong>SAMMANFATTNING</strong></p><p><strong>Syfte: </strong>Syftet med undersökningen var att utvärdera effekterna av behandlingen i projektet ”Rehabilitering med samtalsterapi och yoga” med avseende på upplevt fysiskt, socialt, känslomässigt och funktionellt välbefinnande, samt undersöka deltagarnas tillfredsställelse med rehabiliteringen. <strong>Metod: </strong>Utvärderingen gjordes våren 2010 med kvantitativ metod och deskriptiv, longitudinell design. Alla som skulle börja i nybörjarkursen ombads att delta. Enkäter delades ut före och efter deltagande i max tre rehabiliteringskurser. Deltagarantalet i utvärderingen var 22. Svaren analyserades med hjälp av beskrivande statistik och beroende T-test. <strong>Resultat:</strong> Det kunde inte påvisas några signifikanta skillnader över tid mellan skalorna <em>Fysiskt välbefinnande </em>(p=,507),<em> Socialt välbefinnande </em>(p=,936),<em> Känslomässigt välbefinnande </em>(p=,493)<em> </em>och <em>Funktionellt välbefinnande </em>(p=,388). Vid analys av de enskilda frågorna i skalorna fanns heller inga signifikanta skillnader. Enligt patientutvärderingen ansåg alla deltagare att yoga- och samtalsterapin, i olika grad, har hjälpt dem att hantera sin situation och 95,5% (n=21) säger att de skulle kunna rekommendera denna kurs till en vän i liknande situation. <strong>Slutsats: </strong>Rehabiliteringsprojektet skulle kunna utvecklas ytterligare, men bör fortsätta ges som ett komplement till traditionell onkologisk behandling då den anses vara betydelsefull för deltagarna. P.g.a. brister skulle en ny utvärdering behöva göras.</p> / <p><strong>ABSTRACT</strong></p><p><strong>Aim: </strong>The aim of this study was to evaluate the effects of the treatment in the project “Rehabilitation with psychotherapy and yoga”, regarding physical, emotional, functional and social wellbeing, and to examine the participant’s satisfaction with the rehabilitation. <strong>Method: </strong>The evaluation was done during the spring in 2010 with a quantitative method and descriptive, longitudinal design. Everyone who was to begin the new beginners’ class was asked about participation. Questionnaires were given to the participants, before and after participation in maximum three rehabilitation courses. The number of participants was 22. The answers were analyzed with descriptive statistics and dependent T-test. <strong>Result: </strong>There are no significant differences over time regarding the <em>physical</em> (p=,507), <em>social </em>(p=,936), <em>emotional</em> (p=,493) and <em>functional</em> (p=,388) <em>wellbeing</em> of the participants. When analyzing the unique questions in the wellbeing-scales, no significant differences were found. According to the satisfaction questionnaires, every participants thought that the rehabilitationgroup, in different ways, helped them to cope with their situation and 95,5% (n=21) would recommend this psychotherapy and yoga group to a friend in a similar situation. <strong>Conclusion: </strong>The rehabilitationproject can be improved, but should continue to be provided as a complement to traditional oncological treatment, since it´s considered being of great value for its participants. Because of shortages a new evaluation is motivated.</p>

<p>Esophageal carcinoma is a malignancy with a poor prognosis and is the sixth cause of cancer related death worldwide. In Sweden approximately 400 new cases are diagnosed every year. The aim of this present thesis was to investigate predictive factors for esophageal carcinoma patients.126 esophageal carcinoma patients admitted to the department of Oncology at the University Hospital in Uppsala between 1990-2000 were investigated with focus on known and potential prognostic factors. Performance status and stage of the disease were the only independent prognostic factors (p-values <0.001). </p><p>Angiogenic factors VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p=0.04) whereas bFGF was not (p=0.08) in pre-treatment serum samples from 42 esophageal carcinoma patients. The use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, according to the results from the present study, seems limited. </p><p>HER-2 overexpression was seen in 17% of 97 investigated esophageal tumor samples. In squamous cell carcinoma patients, HER-2 overexpression correlated with poorer survival (p=0.035), whereas in adenocarcinoma patients, HER-2 status did not. HER-2 overexpression seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma. </p><p>Telomerase activity was detected in all esophageal cell lines, with a broad range of activity levels. No correlation was found between telomerase activity levels and sensitivity to investigated cytotoxic drugs. We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines. </p><p>The virus HPV-16 was detected in 16 % of the patients; no other type HPV was detected. HPV-16 infection had no significant effect on survival (p=0.72). Our results did not show that HPV-16 increases survival or improve therapy response in patients with esophageal carcinoma.</p>

<p>Breast cancer mortality in Sweden is now in decline, thanks to early detection and the wide use of adjuvant endocrine therapy and chemotherapy. </p><p>While hormone receptor status is predictive of response to endocrine treatment, there is no clinically useful predictive marker of a patient’s response to chemotherapy. Consequently, patients receive chemotherapy with considerable toxicity but minimal benefit. The aim of this thesis was to investigate a number of methods with the potential to predict response to chemotherapy and thus enhance treatment efficacy in breast cancer patients.</p><p>We found that topo IIα, the key target enzyme of topo II inhibitors, is significantly expressed in nonproliferating breast cancer cells. This finding may explain why topo II inhibitors are effective in patients with slow growing tumors and a low proliferation rate.</p><p>Topo IIα gene amplification was suggestive of increased response to anthracyclines in advanced breast cancer, whereas the oncogene HER2 had no predictive value by itself. These findings are in accordance with current knowledge.</p><p>Cyclin A, a marker of cell proliferation, showed good prognostic value but did not predict response to chemotherapy in advanced breast cancer.</p><p>In vitro chemosensitivity testing with FMCA predicted tumor response in patients with advanced breast cancer with a sensitivity of 89% and a specificity of 53%. Our results are consistent with the results from similar assays, which predict drug resistance with good accuracy while clinical drug sensitivity is less reliably predicted. The use of FMCA and similar assays is not yet recommended outside clinical trials; their main utility is in preclinical testing of new anti-cancer drugs, including targeted therapies.</p><p>The combination of epirubicin, capecitabine, and cisplatin (EXC) demonstrated high clinical response rate (74%) and pathological complete response rate (22%) in locally advanced breast cancer, but with cumbersome toxicity. The fluoropyrimidine biomarkers TS, TP, and DPD did not predict response to the EXC regimen.</p>

In spite of the fact that prostate cancer is the most common male cancer in both Sweden and many other countries in the developed world, little is known of risk factors and predisposing conditions. The only well recognized risk factors are age, race and familial aggregation. More knowledge about risk factors could lead to better preventive measures together with better treatments. One way to evaluate this is to study second primary cancers; the connection between two different cancers can give valuable insight in etiology or clues to shared risk factors. This thesis aims at evaluating risk factors for prostate cancer. We constructed a cohort of 135,713 men diagnosed with prostate cancer and reported to the Swedish Cancer Registry 1958-1996. The cohort was followed for second primary cancers and a doubled risk of male breast cancer was found. We also noted increased risks for small intestine cancers and melanoma. As a follow-up on the increased risk of male breast cancer, we performed a nested case – control study. Included cases were men with first prostate and then breast cancer (n = 41) matched to men with only prostate cancer (n =81). For these men, we collected medical records and extracted data regarding treatment. Furthermore, all men diagnosed with both prostate and breast cancer irrespective which came first (n = 83) were used as probands. To both these sets of cases with breast and prostate cancer, we identified first degree relatives and grandchildren from parish offices throughout Sweden. Linking to the Cancer Registry retrieved all cancer diagnoses amongst relatives. Results from this study show a relation between estrogen treatment of prostate cancer and the risk of developing breast cancer. We also found that a small part of the cases with both cancers appeared in families with inheritance patterns possibly attributed to BRCA2. As estrogen treatment seemed involved in increased risk of breast cancer after prostate cancer, we wanted to investigate the newly discovered Estrogen receptor β and the relation to prostate cancer risk. Previous reports have shown that ERβ acts as a negative regulator of proliferation. ERβ expression occurs mainly in prostatic epithelial cells and the expression gradually diminishes when cancer develops and aggravates. We used a single nucleotide polymorphism (SNP) association study approach to evaluate genetic variation in ERβ as a risk factor for prostate cancer. One SNP, located in the promoter region associated with a small increased risk of prostate cancer whereas variation in the rest of the gene did not. In the last paper, we investigated trans-urethral resection (TURP) of the prostate due to benign prostate hyperplasia (BPH) as a risk factor for later development of prostate cancer. Evidence has gathered that both BPH and prostate cancer are associated to inflammation. By comparing incidence and mortality in a cohort of 7,901 men with the general population there appeared to be an increased risk of prostate cancer but decreased mortality. Analyzing this increased risk further, we conducted a nested case - control study with men extracted from the cohort. Cases had a TURP and later developed prostate cancer and controls just had a TURP. We then evaluated the specimens from TURP regarding extent of inflammation, degree of androgen receptor down regulation and expression of p53, all factors previous associated with prostate cancer. None of these parameters differed between cases and controls and they can therefore not explain the increased risk. Decreased mortality but increased risk might be explained by surveillance bias, which means more medical attention to these patients, resulting in diagnosing clinically non-significant cancers. In summary, our results show a doubled risk of male breast cancer following prostate cancer. A risk that can be attributed to the use of estrogen to treat prostate cancer or to some extent a possible mutation in BRCA2. We also propose that a SNP change in the ERβ promoter confer a small increased risk of prostate cancer. A small risk elevation of prostate cancer following TURP most probable could depend on surveillance bias.

Malignant glioma consists of a group of diseases where the localisation and the nature of the disease makes treatment an extreme challenge. Two important biological features of malignant glioma cells are their infiltrative growth and their ability to induce angiogenesis. Glioma cells migrate extensively behind the blood-brain barrier and infiltrate the surrounding brain making radical treatment with surgery and radiotherapy almost impossible. The aims of this thesis were to investigate factors of importance for glioma cell migration and angiogenesis and to evaluate if an anti-angiogenesis approach alone or in combination with current treatment modalities could inhibit glioma growth. For this purpose we used the BT4C orthotopic rat glioma model and investigated treatment effects of the vascular endothelial growth factor (VEGF) receptor-2 and epidermal growth factor (EGF) receptor tyrosine kinase inhibitor ZD6474 alone or in combination with temozolomide or radiotherapy. Altered protein expression pattern after anti-angiogenesis treatment was measured using a mass-spectrometric proteomic method, followed by multivariate data-analysis. The tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and VEGF showed altered temporal and spatial mRNA expression during glioma progression. In early stages of tumour progression the expression was found throughout the tumour while in later stages, the expression was more predominant in the invasive tumour border. ZD6474 in monotherapy significantly inhibited tumour growth in the BT4C glioma model. The effect was further enhanced when combined with radiotherapy or temozolomide. Using mass-spectrometric methods an altered protein expression pattern after ZD6474 treatment was observed implicating the possibility to use proteomic methods for finding predictive biomarkers for anti-angiogenesis treatment. In conclusion, this thesis demonstrates a co-expression of factors important for glioma growth and angiogenesis and that treatment with an angiogenesis inhibitor has additive effects on glioma growth when combined with radiotherapy and chemotherapy. Finally, an altered protein expression pattern after anti-angiogenesis treatment is evident and detectable. Hopefully this work will contribute to and encourage further research to reach a better understanding of how to combine and evaluate different treatment approaches in malignant glioma.

Astrocytic tumors are the most common malignancies of the central nervous system, accounting for more than 60% of all primary brain tumors. The prognosis for high grade astrocytoma patients is dismal and there is no curative treatment, today. A molecular hallmark of astrocytic tumors is dysregulated receptor tyrosine kinase signaling, especially of the epidermal growth factor receptor (EGFR, ErbB1). The aim of the present thesis was to identify endogenous human proteins that downregulate the function of the ErbB1 receptor. We identified a human gene family, the leucine-rich repeats and immunoglobulin-like domains family (LRIG), consisting of LRIG1, LRIG2 and LRIG3, which might fulfill this criterion. Two candidates were identified, LRIG1 and LRIG2, which genes were localized to regions frequently deleted in human cancers, chromosome bands 3p14 and 1p13, respectively. LRIG1 and LRIG2 mRNA were expressed in all tissues analyzed, with high expression in brain and other organs. The LRIG mRNA were predicted to encode integral membrane proteins. Antibodies against LRIG1 and LRIG2 were developed and the protein expression was analyzed. LRIG1 was found to have an apparent molecular weight of 143 kDa and was expressed in most tissues with high expression in glandular tissues of the breast and prostate, and the peptic cells of the stomach. LRIG2 was slightly smaller and had an apparent molecular weight of 132 kDa. The LRIG proteins were localized to the cell surface and to perinuclear structures, where LRIG1 co-localized with the trans-Golgi network and early endosomes. LRIG1 was found to restrict growth factor signaling by enhancing receptor ubiquitylation and degradation. We showed that LRIG1 interacted with all four members of the ErbB family and induced their downregulation. The interaction with ErbB1 involved both the LRR-domains and the Ig-like domains of LRIG1. LRIG1 enhanced receptor degradation by recruiting the E3 ubiquitin ligase c-Cbl to the LRIG1-ErbB1 complex. LRIG1, LRIG2, and LRIG3 were expressed in glioma cell lines and tumor tissues. The LRIG expression was analyzed in 404 astrocytic tumor samples. We found that perinuclear LRIG protein expression correlated with increased survival of patients with astrocytic tumors. Especially perinuclear LRIG3 showed strong correlations with patient survival and tumor cell proliferation index. In summary, this thesis contains the discovery and characterization of human LRIG1 and LRIG2. LRIG1 was found to interact with ErbB receptors and downregulate their function. In a clinical material, expression of LRIG proteins correlated with survival in patients with astrocytic tumors.

Background: Glioblastoma is the most common and aggressive type of glioma and associated with poor prognosis. Apart from ionizing radiation and some rare genetic disorders, few aetiological factors have been identified for primary brain tumours. Inverse associations to asthma and low IgG levels for varicella zoster virus have in previous studies indicated that the immune system may play a role in glioma development. Little is known about prognostic factors in glioma. Previous studies have shown an association between age, Karnofsky performance status, O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation, and prognosis. Polymorphisms in different low penetrance genes have in some studies been associated with glioma prognosis. Material and methods: In paper I, we analysed IgG levels for four different viruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella zoster virus (VZV) and adenovirus (Ad), in prediagnostic blood samples from 197 cases with glioma and 394 controls collected from three large cohorts: the Northern Sweden Health and Disease Study; the Malmö Diet and Cancer Study; and the Diet, Cancer and Health cohort from Copenhagen. ELISA was used to measure IgG levels and for EBV response to both the nuclear antigen (EBNA1) and the viral capsid antigen (VCA) was measured, for VCA using immunoflourescence. IgG levels were divided into quartiles and binary logistic regression was used to compare the quartiles in cases and controls. All odds ratios were adjusted for age, sex, and cohort. In paper II-IV, we studied 176 glioblastoma cases from Sweden and Denmark. We collected treatment and follow-up data on the cases. We genotyped 30 tagging SNPs in EGF, 89 in EGFR, 27 in VEGFR2, and 17 in VEGF. We also studied 1458 SNPs in 136 DNA repair genes. Hazard ratios were calculated using Cox regression; the major allele was set as categorical variable and all HR were adjusted for age, sex, country, and treatment. For the DNA repair gene results, we adjusted the p-values for multiple testing. Significant findings were confirmed in separate datasets. Results and Discussion: We found a trend towards higher IgG VZV levels in controls compared to glioma cases, especially when restricting the analyses to only include glioma cases with at least 2 years between blood sample and diagnosis. This finding might indicate that there is an aetiological and not a disease-related association. This confirms previous findings and support that a strong immune system can detect and inhibit growth of small cancer clusters. In EGF, we found seven SNPs in one haplotype block that were significantly associated with glioblastoma survival. Four of the SNPs were available for confirmation; however, none reached statistical significance. One explanation could be age differences in the different cohorts. In EGFR, four SNPs associated with survival were found; however, as 89 polymorphisms were tested this was the expected outcome by chance. In VEGF and VEGFR2, we found two SNPs associated with glioblastoma survival, but they could not be confirmed in the separate dataset, and due to multiple testing, were considered to be false positives. Among the DNA repair genes, we found nine SNPs in three genes-MSH2, RAD51L1 and RECQL4-associated with glioblastoma survival after confirmation and adjustment for age, sex, country, and treatment. After adjusting for multiple testing, one SNP in MSH2 and one in RECQL4 remained significant. Conclusions: Our studies provide additional knowledge to the aetiological and prognostic factors important for glioma, emphasising the possible importance of immune function mechanisms. We found limited evidence for the role of genetic variants in glioma progression genes, and some for DNA repair variants as prognostic factors for glioblastoma survival.