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1.	Browall, Maria, et al. (författare) The course of health related quality of life in postmenopausal women with breast cancer from breast surgery and up to five years post-treatment 2013 Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 49, s. S344-S345 Tidskriftsartikel (refereegranskat)abstract Background: Previous studies include too few patients over 70 years to be able to assess treatment effects on Health Related Quality Of Life (HRQOL) in the older age group. We aimed to follow HRQOL in postmenopausal women (55-80 years) with breast cancer receiving adjuvant treatment, until five years post-treatment, and compare with a general population.Patients and methods: The patient sample included 150 women (adjuvant CT n=75 and RT n=75) and two reference samples from the Swedish SF-36 norm database.Results: Data from baseline showed significantly higher levels of physical functioning and general health among the patients compared to the reference sample, and significantly lower levels of bodily pain, emotional role functioning and mental health. Longitudinal analyses showed significant changes in all scales, and three different patterns (a decrease-stable, a decrease-increase, and a stable- increase pattern) were identified.Conclusion: Postmenopausal women seem to successfully manage the effects of adjuvant treatment on HRQOL.
2.	Sjögren, Erik, et al. (författare) Pharmacokinetics of an injectable modified-release 2-hydroxyflutamide formulation in the human prostate gland using a semiphysiologically based biopharmaceutical model. 2014 Ingår i: Molecular pharmaceutics. - : American Chemical Society (ACS). - 1543-8392 .- 1543-8384. ; 11:9, s. 3097-111 Tidskriftsartikel (refereegranskat)abstract The local distribution of 2-hydroxyflutamide (2-HOF) in prostate tissue after a single intraprostatic injection of a novel parenteral modified-release (MR) formulation in patients with localized prostate cancer was estimated using a semiphysiologically based biopharmaceutical model. Plasma concentration-time profiles for 2-HOF were acquired from a phase II study in 24 patients and the dissolution of the MR formulation was investigated in vitro. Human physiological values and the specific physicochemical properties of 2-HOF were obtained from the literature or calculated via established algorithms. A compartmental modeling approach was adopted for tissue and blood in the prostate gland, where the compartments were modeled as a series of concentric spherical shells contouring the centrally positioned depot formulation. Discrete fluid connections between the blood compartments were described by the representative flow of blood, whereas the mass transport of drug from tissue to tissue and tissue to blood was described by a one-dimensional diffusion approximation. An empirical dissolution approach was adopted for the release of 2-HOF from the formulation. The model adequately described the plasma concentration-time profiles of 2-HOF. Predictive simulations indicated that the local tissue concentration of 2-HOF within a distance of 5 mm from the depot formulation was approximately 40 times higher than that of unbound 2-HOF in plasma. The simulations also indicated that spreading the formulation throughout the prostate gland would expose more of the gland and increase the overall release rate of 2-HOF from the given dose. The increased release rate would initially increase the tissue and plasma concentrations but would also reduce the terminal half-life of 2-HOF in plasma. Finally, an in vitro-in vivo correlation of the release of 2-HOF from the parenteral MR formulation was established. This study shows that intraprostatic 2-HOF concentrations are significantly higher than systemic plasma concentrations and that increased distribution of 2-HOF throughout the gland, using strategic imaging-guided administration, is possible. This novel parenteral MR formulation, thus, facilitates good pharmacological effect while minimizing the risk of side effects.
3.	Åström, Fredrik, et al. (författare) Effects of Research Funding, Gender and Type of Position on Research Collaboration Networks: A Micro-level Study of Cancer Research at Lund University 2013 Ingår i: PROCEEDINGS OF ISSI 2013 Vienna: 14th International Society of Scientometrics and Informetrics Conference. - 2175-1935. - 9783200031357 ; , s. 677-689 Konferensbidrag (refereegranskat)abstract The aim of this study is to analyse the extent of which different types of research funding, gender and type of position have an effect on the size and density of research collaboration networks. The material consists of 3,306 documents by scientists doing cancer research at Lund University, indexed in the Web of Science databases. The author and address fields were analysed, by studying frequencies and distribution of authors and organizations, and by conducting co-authorship analyses on the organizational level. The results show substantial differences between scientists with funding from the Swedish Cancer Society (SCS) in comparison with those without SCS funding. When comparing men and women, as well as scientists with preclinical positions and those combining clinical and pre-clinical work; there are larger differences between e.g. women with or without SCS funding than between men and women with SCS funding. The general applicability of these results might be limited; they only take one certain kind of funding into account and they analyses are performed on documents coming out of one particular context. In this case, however, the results suggest that research funding have a larger impact on the size and nature of research collaboration networks than gender or type of position.
4.	Kotronoulas, Grigorios, et al. (författare) Sleep-wake disturbances in patients with cancer and their informal caregivers : A matter of dyads 2012 Ingår i: Forum of Clinical Oncology. - : Hellenic Society of Medical Oncology. - 1792-345X .- 1792-362X. ; 3:1, s. 32-40 Tidskriftsartikel (refereegranskat)abstract Background: Changes in habitual sleep are among the most remarkable and important concerns of both patients with cancer and their informal carers. A dyadic approach in the assessment and management of sleep problems in patients and carers is a promising method of exploring concurrent sleep disturbances and establishing associations between sleep and sleep-impairing factors that may co-vary in the members of the dyad. The purpose of the present mini-review article was to discuss the current evidence, as well as highlight areas where future research is warranted. Patients & Methods: An electronic search for original peer-reviewed articles published between January 1990 and July 2011 in three research and evidence databases (MedLine, CINAHL, EMBASE) was carried out using a wide range of keywords and free-text terms. Cancer care-related evidence was complemented by additional data derived from studies conducted with married couples or in the context of other chronic illnesses. Results: Concurrent and comparable nocturnal sleep disruptions might be evident, where poor sleep quality, decreased sleep duration, and multiple awakenings may correlate with each other within the dyad. Care recipients' and caregivers' night and day rest patterns can be synchronised, as caregivers organise their sleep around the patient. Conclusion: More systematic, dyadic research is warranted to enhance development of intervention protocols for the comprehensive management of sleep disorders in this population throughout the illness experience. These interventions will ensure that sleep patterns are assessed in depth and are managed in a concurrent manner to achieve a concurrent increased level of well-being of patient-caregiver dyads.
5.	Behnam-Motlagh, Parviz, et al. (författare) Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy 2010 Ingår i: Toxins. - Basel : MDPI. - 2072-6651. ; 2:10, s. 2467-2477 Forskningsöversikt (refereegranskat)abstract A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.
6.	Eilegård Wallin, Alexandra, 1975-, et al. (författare) Bereaved siblings' perception of participating in research : a nationwide study 2013 Ingår i: Psycho-Oncology. - : John Wiley & Sons. - 1057-9249 .- 1099-1611. ; 22:2, s. 411-416 Tidskriftsartikel (refereegranskat)abstract ObjectiveThe objective of the present study is to examine bereaved siblings' perception of research participation.MethodsA Swedish nationwide study on avoidable and modifiable health care‐related factors in paediatric oncology among bereaved siblings who lost a brother or sister to cancer between the years 2000 and 2007 was conducted. Data are presented as proportions, and the differences between groups were statistically tested at the 5% significant level using Fisher's exact test.ResultsOut of 240 eligible siblings, 174 responded (73 %). None of the siblings (0/168) thought their participation would affect them negatively in the long term. However, 13% (21/168) stated it was a negative experience to fill out the questionnaire, whereas 84% (142/169) found it to be a positive experience. Women were more likely to report their participation as positive in a long‐term perspective compared with men (p = 0.018).ConclusionsNone of the bereaved siblings in this Swedish nationwide study anticipated any long‐term negative effect from their research participation. A majority reported it as positive to revisit their needs and experiences throughout their brother or sister's illness and death 2–9 years following the loss. We believe that the stepwise approach used in this study contributed to the high acceptance.
7.	Munthe, Christian, 1962 (författare) Burzynski Cancer Clinic Charges Plenty for Entry to Trial of Quack Treatment and Threatens Children and Families of Critical Bloggers 2011 Ingår i: Philosophical Comment Blog. ; :2011-11-28 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
8.	Munthe, Christian, 1962 (författare) Lame Response from the Burzynski Clinic 2011 Ingår i: Philosophical Comment Blog. ; :2011-11-30 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
9.	Lundstrom, Staffan, et al. (författare) Together we can : experiences from 7 years of cross-sectional studies in a Swedish palliative care clinical research network 2010 Ingår i: Palliative Medicine. - : SAGE Publications. - 0269-2163 .- 1477-030X. ; 24:3, s. 261-266 Tidskriftsartikel (refereegranskat)abstract During recent years, research networks and collaboratives focusing on palliative care research have been established both nationally and internationally resulting in several ongoing projects. In 2002, a clinician-based research network, the Palliative Care Research Network in Sweden (PANIS), was established to stimulate research and development of palliative care in Sweden. The growing network, which today includes 60 specialized palliative care units, has used a web-based survey generator to collect data on symptom prevalence, treatment traditions and important issues in palliative care. Eleven different studies involving almost 11,000 patients have been performed within the network including studies on prevalence of antitumoral treatment, the use of opioids, corticosteroids, blood transfusions, parenteral nutrition and prevalence of palliative sedation therapy in specialized palliative care. The working method of the research network is described, and demographic data from 9,298 patients in six cross-sectional studies are presented. Using a relatively simple research methodology, the network has succeeded in addressing key clinical questions and in this article we share experiences and challenges met during the journey.
10.	Tofigh, Ali, et al. (författare) A global structural em algorithm for a model of cancer progression 2011 Ingår i: Adv. Neural Inf. Process. Syst.: Annu. Conf. Neural Inf. Process. Syst., NIPS. - 9781618395993 Konferensbidrag (refereegranskat)abstract Cancer has complex patterns of progression that include converging as well as diverging progressional pathways. Vogelstein's path model of colon cancer was a pioneering contribution to cancer research. Since then, several attempts have been made at obtaining mathematical models of cancer progression, devising learning algorithms, and applying these to cross-sectional data. Beerenwinkel et al. provided, what they coined, EM-like algorithms for Oncogenetic Trees (OTs) and mixtures of such. Given the small size of current and future data sets, it is important to minimize the number of parameters of a model. For this reason, we too focus on tree-based models and introduce Hidden-variable Oncogenetic Trees (HOTs). In contrast to OTs, HOTs allow for errors in the data and thereby provide more realistic modeling. We also design global structural EM algorithms for learning HOTs and mixtures of HOTs (HOT-mixtures). The algorithms are global in the sense that, during the M-step, they find a structure that yields a global maximum of the expected complete log-likelihood rather than merely one that improves it. The algorithm for single HOTs performs very well on reasonable-sized data sets, while that for HOT-mixtures requires data sets of sizes obtainable only with tomorrow's more cost-efficient technologies.
11.	Vassal, Gilles, et al. (författare) Challenges for Children and Adolescents With Cancer in Europe: The SIOP-Europe Agenda 2014 Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 61:9, s. 1551-1557 Tidskriftsartikel (refereegranskat)abstract In Europe, 6,000 young people die of cancer yearly, the commonest disease causing death beyond the age of 1 year. In addition, 300,000-500,000 European citizens are survivors of a childhood cancer and up to 30% of them have severe long-term sequelae of their treatment. Increasing both cure and quality of cure are the two goals of the European paediatric haematology/oncology community. SIOPE coordinates and facilitates research, care and training which are implemented by the 18 European study groups and 23 national paediatric haematology/oncology societies. SIOPE is the European branch of the International Society of Paediatric Oncology and one of the six founding members of the European Cancer Organisation. SIOPE is preparing its strategic agenda to assure long-term sustainability of clinical and translational research in paediatric malignancies over the next 15 years. SIOPE tackles the issues of equal access to standard care and research across Europe and improvement of long term follow up. SIOPE defined a comprehensive syllabus for training European specialists. A strong partnership with parent, patient and survivor organisations is being developed to successfully achieve the goals of this patient-centred agenda. SIOPE is advocating in the field of EU policies, such as the Clinical Trials Regulation and the Paediatric Medicine Regulation, to warrant that the voice of young people is heard and their needs adequately addressed. SIOPE and the European community are entirely committed to the global agenda against childhood cancers to overcome the challenges to increasing both cure and quality of cure of young people with cancer. (c) 2014 Wiley-Liss, Inc., A Wiley Company. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.
12.	Jonsdottir, Kristin, et al. (författare) The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer 2012 Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 135:2, s. 381-390 Tidskriftsartikel (refereegranskat)abstract There is a need for new biomarkers to more correctly identify node-negative breast cancer patients with a good or bad prognosis. Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) is a membrane-bound protein that is associated with cell spreading, integrin activation and exocytosis. Three hundred and five operable T1,2N0M0 lymph node-negative breast cancer patients (median follow-up time 121 months, range 10–178 months) were evaluated for MARCKSL1 expression by immunohistochemistry and quantitative real-time PCR. The results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation), using single (Kaplan–Meier) and multivariate survival analysis (Cox model). Forty-seven patients (15 %) developed distant metastases. With single and multivariate analysis of all features, MARCKSL1 protein expression was the strongest prognosticator (P < 0.001, HR = 5.1, 95 % CI = 2.7–9.8). Patients with high MARCKSL1 expression (n = 23) showed a 44 % survival versus 88 % in patients with low expression at 15-year follow-up. mRNA expression of MARCKSL1 in formalin fixed paraffin-embedded tissue was also prognostic (P = 0.002, HR = 3.6, 95 % CI = 1.5–8.3). However, the prognostic effect of high and low was opposite from the protein expression, i.e., low expression (relative expression ≤ 0.0264, n = 76) showed a 79 % survival versus 92 % in those with high expression of MARCKSL1 mRNA. Multivariate analysis of all features with distant metastases free survival as the end-point showed that the combination of MARCKSL1 protein and phosphohistone H3 (PPH3) has the strongest independent prognostic value. Patients with high expression (≥13) of PPH3 and high MARCKSL1 protein had 45 % survival versus 78 % survival for patients with low MARCKSL1 protein expression and high expression (≥13) of PPH3. In conclusion, MARCKSL1 has strong prognostic value in lymph node-negative breast cancer patients, especially in those with high proliferation.
13.	Gulde, Ingrid, et al. (författare) Palliative Cancer Patients' Experience of Physical Activity 2011 Ingår i: Journal of Palliative Care. - 0825-8597. ; 27:3, s. 296-302 Tidskriftsartikel (refereegranskat)abstract Results from pilot studies indicate that palliative cancer patients report increased well-being and less fatigue after physical activity. This study aimed to explore how palliative cancer patients experienced physical activity. A qualitative design with semi-structured interviews was used. Eleven palliative cancer patients over 18 years old with different diagnoses and Eastern Cooperative Oncology Group Scale performance status levels of between 1 and 3 were interviewed. Four main themes emerged: routines of everyday life, less fatigue, professional guidance, and hope. The first theme comprised two categories: something to do, and being together with others in a similar situation. The theme professional guidance also comprised two categories: the physiotherapist as tutor, and the physiotherapist as motivator. Some cancer patients in palliative care who participated in physical activity experienced less fatigue and enhanced energy. Physical activity helps to bring structure to everyday life and gives a feeling of hope for the future.
14.	Hellström, Andreas, 1972, et al. (författare) A Physician-Led, Learning-Driven Approach to Regional Development of 23 Cancer Pathways in Sweden 2014 Ingår i: Organizing for Sustainable Effectiveness. - 2045-0613 .- 2045-0605. - 9781784410353 - 9781784410346 ; 4, s. 101-131 Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract Purpose This chapter presents a framework for an action research based intervention to develop and transform sustainable healthcare in a regional context. The framework is illustrated by the case of the Regional Cancer Centre (RCC) West in western Sweden.Design/methodology/approach The framework draws upon and develops Pettigrew’s context–content–process model of strategic change and applies it to the unfolding narrative of the change effort. The empirical focus is the activities of a learning platform consisting of the RCC leadership, senior cancer physicians designated as process owners and an action research team. Data were collected from documents, observations of the learning platform, notes from meetings and interviews. Outcome data were obtained via the self-reporting of the physicians.Findings The learning platform established the capability for wide ranging development and quality improvement on the 23 cancer pathways as well as some support activities around principles of patient-centred care. A clear result is greater inter-organisational collaboration between care professionals as well as the introduction of new medicines, clinical methods, joint learning activities and new forms of measurement and monitoring of care practices. All of the improved measures are sustained.Originality/value Whilst there is no shortage of rhetoric on patient-centred care, the reality is that in complex healthcare systems solutions such as process-oriented approaches often fail. This case presents a model and an approach that eschews clear visions for change and instead places an emphasis on dialogue, participation, professional autonomy and collaborative communities as means for achieving the patient-centred ideal. The case also shows the value of seeing sustainable health systems as being grounded on practitioner–scholar collaboration that combines practical knowing with scientific knowledge.
15.	Johansson, K., et al. (författare) Moving between rooms - moving between life and death: nurses' experiences of caring for terminally ill patients in hospitals 2012 Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 21:13-14, s. 2034-2043 Tidskriftsartikel (refereegranskat)abstract Aim. This study describes the meanings of generalist registered nurses experiences of caring for palliative care patients on general wards in hospitals. Background. Earlier research shows that work with patients in palliative care is demanding. More research concerning palliative care is undertaken in oncological care, in hospice and in home-care settings than in general wards. It is therefore important to examine the palliative care in the context of acute-care settings to discover more about this phenomenon, to understand the experiences of nurses in this situation and to develop patient care. Design. Qualitative, descriptive and interpretive study. Method. Eight registered nurses in two different hospitals in Sweden were interviewed. The patients on these wards suffered from surgical and medical conditions, i.e. both curative and palliative care were administered. The interviews were analysed using a phenomenological hermeneutical approach inspired by Ricoeurs philosophy. Results. The registered nurses experiences are presented as seven themes and a comprehensive, interpreted whole. This latter revealed the significance of contrasts, contradictions and movement between the material and psychological experiences of the room and nursing care in this care context. Conclusions. The registered nurses say that something momentous occurred during the care process and they showed a strong determination and commitment to being part of the ending of the patients life circle, despite the situation often being one of stress. Relevance to clinical practice. The findings highlight the need for various forms of support for the nurses to meet their need for new and updated knowledge and support in existential matters. This may promote a better quality of care and confirm the nurses in their caring practice. Moreover, there is a need to introduce the hospice philosophy into acute-care settings in hospitals.
16.	Petersen, Helle Vendel, et al. (författare) Balancing Life with an Increased Risk of Cancer: Lived Experiences in Healthy Individuals with Lynch Syndrome 2014 Ingår i: Journal of Genetic Counseling. - : Wiley. - 1059-7700 .- 1573-3599. ; 23:5, s. 778-784 Tidskriftsartikel (refereegranskat)abstract Possibilities to undergo predictive genetic testing for cancer have expanded, which implies that an increasing number of healthy individuals will learn about cancer predisposition. Knowledge about how an increased risk of disease influences life in a long-term perspective is largely unknown, which led us to explore lived experiences in healthy mutation carriers with Lynch syndrome. Individual interviews were subjected to descriptive phenomenological analysis. Four constitutions, namely, family context, interpretation and transformation, approach to risk and balancing life at risk were identified and formed the essence of the phenomenon "living with knowledge about risk." Family context influences how experiences and knowledge are interpreted and transformed into thoughts and feelings, which relates to how risk is approached and handled. The constitutions influence each other in a dynamic relationship and create a balancing act between anxiety and worry and feelings of being safe and in control.
17.	Room, Robin, et al. (författare) Alcohol and non-communicable diseases-cancer, heart disease and more 2011 Ingår i: Addiction. - : Wiley. - 0965-2140 .- 1360-0443. ; 106:1, s. 1-2 Tidskriftsartikel (refereegranskat)
18.	Alevronta, Eleftheria, et al. (författare) Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy 2010 Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 97:1, s. 54-59 Tidskriftsartikel (refereegranskat)abstract Background and purpose: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. Material and methods: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. Results: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D-50 = 61.5 Gy (52.9-84.9 Gy), gamma = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3). Conclusions: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.
19.	Aydin, Denis, et al. (författare) Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study. 2011 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 103:16, s. 1264-76 Tidskriftsartikel (refereegranskat)abstract It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents.
20.	Branstrom, Richard, et al. (författare) Perceptions of genetic research and testing among members of families with an increased risk of malignant melanoma 2012 Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48:16, s. 3052-3062 Tidskriftsartikel (refereegranskat)abstract Background: Several melanoma susceptibility genes have been identified. As part of the international genetic research programme of the GenoMEL consortiums research on genetic mutations in melanoma families, the aim of this study was to examine family members' views about their risk of melanoma, gene testing and genetic research. Methods: Self-report data were gathered using online and paper-based surveys available in four languages among 312 individuals (62% from Europe, 18% from Australia, 13% from the United States of America (USA) and 7% from Israel). Results: Fifty three percent had been diagnosed with a melanoma, and 12% had a positive susceptibility gene test result. Respondents with many moles and freckles were more likely to perceive themselves at risk for developing melanoma (odds ratio [OR](Freckles) = 2.24 with 95% confidence interval [CI] = 1.18-4.26; ORMany (moles) = 6.92, 95% CI = 2.37-20.23). Respondents who had received a non-informative (negative) genetic test result were much less likely to perceive themselves at increased risk (OR = 0.17, 95% CI = 0.04-0.73). Safe-guards were perceived as important to protect genetic information, but there was also support for the storage and exchange of such information. Overall, respondents were in favour of genetic testing, even if current knowledge about melanoma risk genes is still limited. Contrary to previous studies, participants reported that a non-informative (negative) genetic test result, although not necessarily indicative of lower risk of melanoma, would be likely to reduce their practise of preventive behaviours. Conclusions: Participants were influenced by their phenotype and test results in risk estimations. They expressed positive views on genetic research and towards genetic testing, but reported that a non-informative (negative) test result might be associated with an (erroneous) perception of reduced risk and fewer preventive behaviours. These results highlight the urgency of improving the quality of genetic counselling and increasing the effectiveness of communication regarding genetic test results. (C) 2012 Elsevier Ltd. All rights reserved.
21.	Hemmingsson, Oskar, 1975- (författare) ASNA1 and cisplatin resistance : studies in C. elegans and in human tumor cells 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Platinum based chemotherapy is widely used to treat cancer. Cisplatin (diamminedichloroplatinum) combination treatments provide cure for metastatic testicular cancer and prolong survival for patients suffering from ovarian, head and neck, bladder and non small cell lung cancer. Tumors that initially respond to treatment may eventually acquire resistance, resulting in treatment failure. Cisplatin resistant cells are crossresistant to arsenite and antimonite and these metalloids are exported from bacteria by the ars-operon. In this thesis, we describe the human ArsA homolog, ASNA1, as a protein involved in a novel resistance mechanism to cisplatin, arsenite and antimonite. ASNA1 was downregulated by antisense and siRNA techniques in human melanoma and ovarian carcinoma cell lines. These cells displayed increased sensitivity to arsenite and the platinum based drugs cisplatin, carboplatin and oxaliplatin. In both melanoma and ovarian carcinoma, cisplatin resistant cells overexpressed ASNA1. Blockage of ASNA1 resulted in increased apoptosis and retarded growth, complicating further characterization of ASNA1 in human cell lines. ASNA1 also promotes insulin signaling and mediates membrane insertion of tail-anchored proteins. To explore different aspects of ASNA1 function with respect to cisplatin resistance, we used the model organism C. elegans. In the nematode C. elegans, asna-1 (rnai) treated larvae were hypersensitive to cisplatin, arsenite and antimonite. Adult asna-1 mutant worms were cisplatin sensitive and this hypersensitivity was seen even when apoptosis was blocked. Expression of human ASNA1 rescued the cisplatin hypersensitivity in asna-1 mutants, showing conservation of function. Transgene expression of mutated forms of asna-1 separated the cisplatin hypersensitivity phenotype from the insulin signaling phenotype of asna-1 mutants. Three ASNA-1 residues, His164, Cys285 and Cys288 were identified as essential for ASNA-1 promoted cisplatin resistance but not for insulin signaling. Finally, studies of the C. elegans germline revealed increased numbers of apoptotic cells in asna-1 mutants. In conclusion, C. elegans is a suitable model organism to identify and characterize cisplatin response mechanisms. A targeted therapy against ASNA1 could sensitize cisplatin resistant cells and improve outcome for cancer patients.
22.	Mu, Yabing, et al. (författare) TRAF6 ubiquitinates TGFβ type I receptor to promote its cleavage and nuclear translocation in cancer 2011 Ingår i: Nature Communications. - London : Macmillan Publishers Limited. - 2041-1723. ; 2:330 Tidskriftsartikel (refereegranskat)abstract Transforming growth factor β (TGFβ) is a pluripotent cytokine promoting epithelial cell plasticity during morphogenesis and tumour progression. TGFβ binding to type II and type I serine/threonine kinase receptors (TβRII and TβRI) causes activation of different intracellular signaling pathways. TβRI is associated with the ubiquitin ligase tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6). Here we show that TGFβ, via TRAF6, causes Lys63-linked polyubiquitination of TβRI, promoting cleavage of TβRI by TNF-alpha converting enzyme (TACE), in a PKCζ-dependent manner. The liberated intracellular domain (ICD) of TβRI associates with the transcriptional regulator p300 to activate genes involved in tumour cell invasiveness, such as Snail and MMP2. Moreover, TGFβ-induced invasion of cancer cells is TACE- and PKCζ- dependent and the TβRI ICD is localized in the nuclei of different kinds of tumour cells in tissue sections. Thus, our data reveal a specific role for TβRI in TGFβ mediated tumour invasion.
23.	Omerov, Pernilla, et al. (författare) Preparatory Studies to a Population-Based Survey of Suicide-Bereaved Parents in Sweden. 2013 Ingår i: Crisis. - : Hogrefe Publishing Group. - 0227-5910 .- 2151-2396. ; 34:3, s. 200-210 Tidskriftsartikel (refereegranskat)abstract Background: There is a need for evidence-based guidelines on how professionals should act following a suicide. In an effort to provide empiric knowledge, we designed a nationwide population-based study including suicide-bereaved parents. Aim: To describe the process from creating hypotheses through interviews to the development of a population-based questionnaire. Method: We used interviews, qualitative analysis and various means of validation to create a study-specific questionnaire to be used in a nonselected nationwide population of suicide-bereaved parents and a control population of nonbereaved (N = 2:1). The Swedish Register of Causes of Death and the Multigeneration Register were used to identify eligible individuals. All presumptive participants received a letter of invitation followed by a personal contact. Results: We developed a questionnaire covering the participants' perception of participation, their daily living, psychological morbidity, professional actions, and other experiences in immediate connection to the time before and after the suicide. Almost three out of four parents (bereaved = 666, nonbereaved = 377) responded to the questionnaire. Conclusions: By involving parents early in the research process we were able to create a questionnaire that generated a high participation rate in a nationwide population-based study that might help us to answer our hypotheses about bereavement after suicide.
24.	Stattin, Pär, et al. (författare) Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. 2010 Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102:13, s. 950-8 Tidskriftsartikel (refereegranskat)abstract Treatment for localized prostate cancer remains controversial. To our knowledge, there are no outcome studies from contemporary population-based cohorts that include data on stage, Gleason score, and serum levels of prostate-specific antigen (PSA).
25.	Fallbjörk, Ulrika, 1967-, et al. (författare) A preliminary study into women's experiences of undergoing reconstructive surgery after breast cancer 2012 Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 16:3, s. 220-226 Tidskriftsartikel (refereegranskat)abstract Breast cancer is the most common type of cancer among women. In Sweden, about 40% of women diagnosed with breast cancer undergo a mastectomy; breast reconstruction (BR) may be an option for these women. However, the experience of undergoing reconstructive surgery appears to be only very scarcely researched, despite its importance in clinical nursing.Aim: The purpose of this study was to explore women's experiences of undergoing breast reconstructive surgery after mastectomy due to breast cancer.Methods: Six women participated in narrative interviews about their experiences of reconstructive surgery, and the interview data were analysed using thematic narrative analysis.Results: All six women were unprepared for the strenuous experience of undergoing a BR. They described the process as difficult and painful, entailing several operations and an unexpectedly long recovery period. They were also unprepared for how arduous it would be, both physically and emotionally. However, getting a BR had been important to all the women. The BR process was captured in four themes: (1) uninformed care; (2) arduous experiences; (3) body alterations; and (4) moving on.Conclusions: Obtaining adequate information and being involved in the decision-making process along the pathway of a BR could help the women to prepare physically and emotionally for the strenuous experiences related to reconstructive surgery.
26.	Fallbjörk, Ulrika, 1967- (författare) I spåren av bröstcancer : att leva med eller utan ett rekonstruerat bröst efter mastektomi 2012 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Bakgrund: I Sverige är bröstcancer den vanligaste formen av kvinnlig cancer och utgör nära en tredjedel av kvinnlig cancer. I behandlingen av bröstcancer har kirurgi en betydande roll. Nära hälften av kvinnorna genomgår mastektomi, men det finns en stor variation inom landet. Att förlora ett bröst efter mastektomi har såväl en kroppslig som psykologisk innebörd. Avhandlingen omfattar fyra delstudier som beskriver detta på olika sätt.Syfte: Det övergripande syftet med avhandlingen är att studera betydelsen av att förlora ett bröst på grund av cancersjukdom samt motiv och beslutsprocess i ställningstagande till att leva med eller utan ett rekonstruerat bröst.Metod: Avhandlingen baseras på två populationer av kvinnor boende i norra Sverige som genomgått mastektomi på grund av bröstcancer: de kvinnor som genomgått mastektomi under 2003 (delstudie I–III) samt de kvinnor som genomgått mastektomi mellan oktober 2006 och september 2007 (delstudie IV). Dessa kvinnor identifierades via det regionala cancerregistret, onkologiskt centrum, Norrlands universitetssjukhus. Statistiska analyser genomfördes i delstudie I och IV och tematisk narrativ analys har tillämpats i delstudie II och III.Resultat: Delstudie I: År 2007 skickades ett nykonstruerat självskattningsformulär ”Life After Mastectomy” (LAM) ut till 149 kvinnor varav 85% (n=126) besvarades. Av dessa kvinnor hade 25% genomgått bröstrekonstruktion. Resultaten av en multipel regressionsanalys visade att bröstrekonstruktion var signifikant relaterat till lägre ålder, känsla av att vara attraktiv och sexuellt intresse. För att få en djupare och mer nyanserad förståelse kring innebörder av att förlora ett bröst efter mastektomi och motiv till att avstå från eller genomgå bröstrekonstruktion gjordes ett strategiskt urval av 15 kvinnor från delstudie I som deltog i en forskningsintervju(delstudie II). I den tematiska narrativa analysen identifierades tre typberättelser. I den första typberättelsen beskrevs mastektomin som ”no big deal” och att genomgå en bröstrekonstruktion var inte ens värt att överväga. I den andra typberättelsen beskrevs mastektomin som ”att förlora sig själv” och en bröstrekonstruktion beskrevs som ett sätt att återställa sig som person, kvinna och sexuell varelse. Den tredje typberättelsen intog en position mellan ”no big deal” och ”att förlora sig själv” och en bröstrekonstruktion beskrevs som ett välkommet erbjudande vilket gjorde det enklare att se och känna sig som kvinna. I delstudie III undersöktes sex kvinnors erfarenheter av att genomgå bröstrekonstruktion. Samtliga kvinnor var oförberedda på den krävande procedur som de genomgick. De beskrev processen som svår och smärtsam med upprepade operationer och en oväntat lång konvalescenstid. Även om kvinnorna var oförberedda på hur tufft det skulle komma att bli både fysiskt och emotionellt beskrevs bröstrekonstruktionen som betydelsefull för dem. Delstudie IV: I denna uppföljningsstudie inkluderades kvinnorna 10 månader efter mastektomin då självskattningsformuläret LAM skickades ut. Datainsamlingen med samma formulär upprepades två år senare (tre år efter mastektomin). Kvinnornas (n=76) känsla av attraktivitet och kvinnlighet hade inte förändrats mellan de två mättillfällena, med undantag för vissa aspekter av sexualitet som hade försämrats. Vid uppföljningen hade 21% av kvinnorna genomgått bröstrekonstruktion och dessa kvinnor var yngre. I övrigt kundeinga signifikanta skillnader ses mellan de kvinnor som genomgått respektiveej genomgått bröstrekonstruktion.Slutsats: Denna avhandling ger en inblick i betydelsen av att förlora ett bröst efter mastektomi. Att förlora ett bröst efter mastektomi kan vara av mindre eller större betydelse. För de kvinnor som upplevde bröstförlusten som en förlust av sig själva, kom en bröstrekonstruktion att betraktas som en livsnödvändighet (delstudie II). De flesta av kvinnorna 75% i delstudie I och 79% i delstudie IV genomgick inte någon bröstrekonstruktion. De kvinnor som genomgick rekonstruktiv kirurgi beskrev proceduren som svår fysiskt och emotionellt, men trots detta sågs den som viktig för dem (delstudie III). Vid uppföljningen i delstudie IV, var kvinnornas upplevelse av attraktivitet och kvinnlighet oförändrade, men upplevelsen av att känna sig bekväm vid sexuell intimitet utvecklades negativt. Detta var oberoende av om kvinnan genomgått bröstrekonstruktion eller inte, vilket kan ses som överraskande. Det är viktigt att som sjukvårdpersonal uppmärksamma hur den enskilda kvinnan själv upplever betydelsen av att ha förlorat ett bröst för att inte låta sig styras av vaga schabloner kring relationen bröst–sexualitet–kvinnlighet.
27.	Hansson, Anders, 1953-, et al. (författare) Opening Pandora's box: The experiences of having an asymptomatic aortic aneurysm under surveillance 2012 Ingår i: Health Risk & Society. - : Informa UK Limited. - 1369-8575 .- 1469-8331. ; 14:4, s. 341-359 Tidskriftsartikel (refereegranskat)abstract Abdominal aortic aneurysm (AAA) is a ballooning-out of the aorta that does not normally give any symptoms. Undetected and untreated an aortic aneurysm can rupture, which in most cases is fatal. Mass screening of 65-year old men for the early detection of AAA and, in selected cases, operation seem to reduce mortality due to rupture, although, screening has not reduced the overall mortality in this group. In Vastra Gotaland, the southwest part of Sweden, screening for AAA amongst 65-year old men started in 2009. There are controversies within the medical community about the benefits and adverse effects of screening. In order to explore men's experiences of being screened and knowing they had an aortic aneurysm, we undertook a qualitative interview study with 15 men who in the screening programme were identified as having an aortic aneurysm and who were to be followed-up with annual ultrasonic examinations for an indeterminate number of years. The interviews were analysed for categories and themes using content analysis. The study found that the men were ambivalent about the knowledge that they had an AAA and about the follow-up monitoring. They appreciated having the knowledge but it was accompanied by worry, feelings of anxiety and existential thoughts about the fragility and finiteness of life. We recommend that before a screening programme is implemented, the psycho-social consequences should be thoroughly investigated. Participants should be given adequate and understandable information about the consequences of screening so that they can make an informed choice whether to participate or not.
28.	Jarynowski, Andrzej, et al. (författare) Studying Possible Outcomes in a Model of Sexually Transmitted Virus (HPV) Causing Cervical Cancer for Poland 2014 Ingår i: Advances in Social Simulation. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642398285 - 9783642398292 ; , s. 129-141 Bokkapitel (refereegranskat)abstract The aim of this paper is to supplement knowledge about the spread of sexually transmitted diseases through computer simulations. The model has aggregated the most important properties of HPV infections and development of cervical cancer in demographically changing Polish society. The main goal is the authoritative analysis of the potential epidemiological control strategies and their impact on situation in Poland in the future 25 years. Constructed model shows indication that vaccination with screening organized alongside would be effective measures against cervical cancer. It also alarms authorities that processes like aging of society and increase of sexual activity (which are taking place in Poland at the moment) could recall epidemic, if prevention would not act properly.
29.	Nilsson, J., et al. (författare) 'Will I be able to have a baby?' Results from online focus group discussions with childhood cancer survivors in Sweden 2014 Ingår i: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 29:12, s. 2704-2711 Tidskriftsartikel (refereegranskat)abstract STUDY QUESTION: What do adolescent and young adult survivors of childhood cancer think about the risk of being infertile?SUMMARY ANSWER: The potential infertility, as well as the experience of having had cancer, affects well-being, intimate relationships and the desire to have children in the future.WHAT IS KNOWN ALREADY: Many childhood cancer survivors want to have children and worry about possible infertility.STUDY DESIGN, SIZE, DURATION: For this qualitative study with a cross-sectional design, data were collected through 39 online focus group discussions during 2013.PARTICIPANTS/MATERIALS, SETTING, METHODS: Cancer survivors previously treated for selected diagnoses were identified from The Swedish Childhood Cancer Register (16-24 years old at inclusion, ≥5 years after diagnosis) and approached regarding study participation. Online focus group discussions of mixed sex (n = 133) were performed on a chat platform in real time. Texts from the group discussions were analysed using qualitative content analysis.MAIN RESULTS AND THE ROLE OF CHANCE: The analysis resulted in the main category Is it possible to have a baby? including five generic categories: Risk of infertility affects well-being, Dealing with possible infertility, Disclosure of possible infertility is a challenge, Issues related to heredity and Parenthood may be affected. The risk of infertility was described as having a negative impact on well-being and intimate relationships. Furthermore, the participants described hesitation about becoming a parent due to perceived or anticipated physical and psychological consequences of having had cancer.LIMITATIONS, REASONS FOR CAUTION: Given the sensitive topic of the study, the response rate (36%) is considered acceptable. The sample included participants who varied with regard to received fertility-related information, current fertility status and concerns related to the risk of being infertile.WIDER IMPLICATIONS OF THE FINDINGS: The results may be transferred to similar contexts with other groups of patients of childbearing age and a risk of impaired fertility due to disease. The findings imply that achieving parenthood, whether or not with biological children, is an area that needs to be addressed by health care services.STUDY FUNDING/COMPETING INTERESTS: The study was financially supported by The Cancer Research Foundations of Radiumhemmet, The Swedish Childhood Cancer Foundation and the Doctoral School in Health Care Science, Karolinska Institutet. The authors report no conflicts of interest.
30.	Schenkman, Bo, et al. (författare) Color interaction – theory, examples and applications 2011 Ingår i: Encyclopedia of Eye Research. - Hauppauge : Nova Publishers. - 9781617618345 Bokkapitel (refereegranskat)abstract Color interaction is a perceptual effect that will influence how color combinations appear to an observer. Two main categories are color induction and color assimilation, the former when two colors become more different looking, and the latter when two colors become more similar looking. Typical examples are presentations of web pages on computer displays, cartographic pictures and maps, artistic displays such as paintings, and of environmental images, such as colors on houses. In this survey of concepts and research, the focus is on fundamental issues and definitions regarding these effects. The emphasis is on modern types of displays and relevant characteristics of different technologies are also given. Some historic perspectives are included. Different color appearance models and how they take color interaction into consideration are discussed, also including information on suitable possible color adjustments that the models may give. References are made to modern visual perceptual theories, and the place of these effects in a broader perceptual theory is considered. A number of illusions and pictures that illustrate interaction effects are included. As an example an experiment with perceived interactions between geometrical objects is described in short. Six observation colors and three interaction colors for each observed color were presented to ten observers, who performed a matching task. The result of this study is presented as color interaction diagrams in the CIELUV color space. The importance of color and color interaction in different applications is discussed together with a set of guidelines. The advantages and disadvantages that may result from using the guidelines are addressed. Some concluding remarks on possible future work in color interaction are given.
31.	Senn, B, et al. (författare) How cancer research could benefit from the Complex Intervention Framework : students' experiences of the European Academy of Nursing Science summer school 2011 Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 0961-5423 .- 1365-2354. ; 20:1, s. 1-4 Tidskriftsartikel (refereegranskat)
32.	Zwierzina, Heinz, et al. (författare) Molecularly targeted therapies for colorectal cancer: Strategies for implementing translational research in clinical trials 2010 Ingår i: CURRENT OPINION IN MOLECULAR THERAPEUTICS. - : Thomson Scientific. - 1464-8431. ; 12:6, s. 703-711 Forskningsöversikt (refereegranskat)abstract Few breakthroughs in preclinical research have translated into meaningful benefits, either in clinical terms or quality of life, for patients with advanced colorectal cancer, despite important preclinical discoveries regarding aberrant biological pathways associated with disease development and progression. The many reasons for the slow progress are diverse, ranging from the failure to codevelop biomarkers and targeted therapies, the regulatory burdens imposed on academic investigators, and the failure to collect serial tumor biopsies during clinical trials. This review discusses promising translational research that could help reduce the disparity between preclinical discovery and patient benefit, and advocate the concentration of efforts and resources on the most promising therapeutic targets in colorectal cancer, such as EGFR, VEGF and Fc gamma receptor.
33.	Börjeson, Sussanne, et al. (författare) State of Science Conference in Cancer Care - identification of front line research topics 2010 Ingår i: Acta Oncologica. - London, United Kingdom : Informa Healthcare. - 0284-186X .- 1651-226X. ; 49:2, s. 134-135 Tidskriftsartikel (refereegranskat)
34.	Castaño, Zafira, et al. (författare) Stromal EGF and igf-I together modulate plasticity of disseminated triple-negative breast tumors 2013 Ingår i: Cancer Discovery. - 2159-8274. ; 3:8, s. 922-935 Tidskriftsartikel (refereegranskat)abstract The causes for malignant progression of disseminated tumors and the reasons recurrence rates differ in women with different breast cancer subtypes are unknown. Here, we report novel mechanisms of tumor plasticity that are mandated by microenvironmental factors and show that recurrence rates are not strictly due to cell-intrinsic properties. Specifically, outgrowth of the same population of incipient tumors is accelerated in mice with triple-negative breast cancer (TNBC) relative to those with luminal breast cancer. Systemic signals provided by overt TNBCs cause the formation of a tumor-supportive microenvironment enriched for EGF and insulin-like growth factor-I (IGF-I) at distant indolent tumor sites. Bioavailability of EGF and IGF-I enhances the expression of transcription factors associated with pluripotency, proliferation, and epithelial-mesenchymal transition. Combinatorial therapy with EGF receptor and IGF-I receptor inhibitors prevents malignant progression. These results suggest that plasticity and recurrence rates can be dictated by host systemic factors and offer novel therapeutic potential for patients with TNBC.
35.	Davies, John R, et al. (författare) Inherited variation in the PARP1 gene and survival from melanoma 2014 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:7, s. 1625-1633 Tidskriftsartikel (refereegranskat)abstract We report the association of an inherited variant located upstream of the poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) gene (rs2249844), with survival in 11 BioGenoMEL melanoma cohorts. The gene encodes a protein involved in a number of cellular processes including single-strand DNA repair. Survival analysis was conducted for each cohort using proportional hazards regression adjusting for factors known to be associated with survival. Survival was measured as overall survival (OS) and, where available, melanoma-specific survival (MSS). Results were combined using random effects meta-analysis. Evidence for a role of the PARP1 protein in melanoma ulceration and survival was investigated by testing gene expression levels taken from formalin-fixed paraffin-embedded tumors. A significant association was seen for inheritance of the rarer variant of PARP1, rs2249844 with OS (hazard ratio (HR) = 1.16 per allele, 95% confidence interval (CI) 1.04-1.28, p=0.005, eleven cohorts) and MSS (HR=1.20 per allele, 95% CI 1.01-1.39, p=0.03, eight cohorts). We report bioinformatic data supportive of a functional effect for rs2249844. Higher levels of PARP1 gene expression in tumors were shown to be associated with tumor ulceration and poorer OS. What's new? Although staging systems predict outcome fairly well for melanoma, survival still varies among individual patients. In this meta-analysis, the authors found that inheritance of a rare genetic variant of PARP1 was associated with improved survival of melanoma patients. Increased expression of PARP1 has been associated with poorer outcome, and depletion of PARP1 may reduce both melanoma growth and angiogenesis. The identification of this and other germline variants that affect survival may help to identify key biological pathways active in host/tumor interactions, which may lead to the discovery of new therapeutic targets for treating advanced melanoma. Epidemiology
36.	Johansson, Birgitta, et al. (författare) Editorial comment on "Disregarding clinical trial-based patient-reported outcomes is unwarranted : Five advances to substantiate the scientific stringency of quality-of-life measurement". 2010 Ingår i: Acta Oncologica. - Oslo, Norway : Taylor & Francis. - 0284-186X .- 1651-226X. ; 49:2, s. 163-165 Tidskriftsartikel (refereegranskat)
37.	Marko-Varga, György, et al. (författare) Standardization and Utilization of Biobank Resources in Clinical Protein Sciene with Examples of Emerging Applications 2012 Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:11, s. 5124-5134 Tidskriftsartikel (refereegranskat)abstract Biobanks are a major resource to access and measure biological constituents that can be used to monitor the status of health and disease, both in unique individual samples and within populations. Most “omic” activities rely on access to these collections of stored samples to provide the basis for establishing the ranges and frequencies of expression. Furthermore, information about the relative abundance and form of protein constituents found in stored samples provides an important historical index for comparative studies of inherited, epidemic, and developing disease. Standardizations of sample quality, form, and analysis are an important unmet need and requirement for gaining full benefit from collected samples. Coupled to this standard is the provision of annotation describing clinical status and metadata of measurements of clinical phenotype that characterizes the sample. Today we have not yet achieved consensus on how to collect, manage, and build biobank archives in order to reach goals where these efforts are translated into value for the patient. Several initiatives (OBBR, ISBER, BBMRI) that disseminate best practice examples for biobanking are expected to play an important role in ensuring the need to preserve the sample integrity of biosamples stored for periods that reach one or several decades. These developments will be of great value and importance to programs such as the Chromosome Human Protein Project (C-HPP) that will associate protein expression in healthy and disease states with genetic foci along of each of the human chromosomes.
38.	Becker, Claudia, et al. (författare) Cancer risk in association with Parkinson disease: A population-based study 2010 Ingår i: PARKINSONISM & RELATED DISORDERS. - 1353-8020. ; 16:3, s. 186-190 Tidskriftsartikel (refereegranskat)
39.	Cernvall, Martin, 1980-, et al. (författare) The factor structure of traumatic stress in parents of children with cancer : A longitudinal analysis 2012 Ingår i: Journal of Pediatric Psychology. - : Oxford University Press (OUP). - 0146-8693 .- 1465-735X. ; 37:4, s. 448-457 Tidskriftsartikel (refereegranskat)abstract Objectives To determine the factor structure of posttraumatic stress symptoms (PTSS) and assess its stability over time among parents of children diagnosed with cancer. Methods Parents of children with cancer included in a longitudinal study completed the posttraumatic stress disorder (PTSD) Checklist–Civilian Version 2 weeks (n = 249) and 2 (n = 234) and 4 (n = 203) months after their child's diagnosis. Confirmatory factor analysis (CFA) was used to assess 3 models of the underlying dimensions of PTSD and invariance tests were used to assess stability over time. Results A longitudinal CFA with the factors reexperiencing, avoidance, dysphoria, and hyperarousal provided best fit to the data. Invariance testing suggested that the pattern and size of loadings were equivalent across the three assessments. Discussions Findings tentatively suggest that PTSS among parents of children with cancer consist of four factors. Implications for research and clinical practice are discussed.
40.	Schoenrock, A., et al. (författare) Efficient prediction of human protein-protein interactions at a global scale 2014 Ingår i: Bmc Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods. Results: On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.1%, we predicted 172,132 putative PPIs. We demonstrate the usefulness of these predictions through a range of experiments. Conclusions: The speed and accuracy associated with MP-PIPE can make this a potential tool to study individual human PPI networks (from genomic sequences alone) for personalized medicine.
41.	Brändstedt, Jenny, et al. (författare) Associations of anthropometric factors with KRAS and BRAF mutation status of primary colorectal cancer in men and women : a cohort study 2014 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. 98964-98964 Tidskriftsartikel (refereegranskat)abstract Obesity is a well-established risk factor for colorectal cancer (CRC), and accumulating evidence suggests a differential influence of sex and anthropometric factors on the molecular carcinogenesis of the disease. The aim of the present study was to investigate the relationship between height, weight, bodyfat percentage, waist- and hip circumference, waist-hip ratio (WHR), body mass index (BMI) and CRC risk according to KRAS and BRAF mutation status of the tumours, with particular reference to potential sex differences. KRAS and BRAF mutations were analysed by pyrosequencing in tumours from 494 incident CRC cases in the Malmö Diet and Cancer Study. Hazard ratios of CRC risk according to anthropometric factors and mutation status were calculated using multivariate Cox regression models. While all anthropometric measures except height were associated with an increased risk of KRAS-mutated tumours, only BMI was associated with an increased risk of KRAS wild type tumours overall. High weight, hip, waist, WHR and BMI were associated with an increased risk of BRAF wild type tumours, but none of the anthropometric factors were associated with risk of BRAF-mutated CRC, neither in the overall nor in the sex-stratified analysis. In men, several anthropometric measures were associated with both KRAS-mutated and KRAS wild type tumours. In women, only a high WHR was significantly associated with an increased risk of KRAS-mutated CRC. A significant interaction was found between sex and BMI with respect to risk of KRAS-mutated tumours. In men, all anthropometric factors except height were associated with an increased risk of BRAF wild type tumours, whereas in women, only bodyfat percentage was associated with an increased risk of BRAF wild type tumours. The results from this prospective cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis, defined by KRAS and BRAF mutation status of the tumours.
42.	Brändstedt, Jenny, et al. (författare) Associations of hormone replacement therapy and oral contraceptives with risk of colorectal cancer defined by clinicopathological factors, beta-catenin alterations, expression of cyclin D1, p53, and microsatellite-instability 2014 Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Postmenopausal hormone therapy (HRT) and oral contraceptive (OC) use have in several studies been reported to be associated with a decreased colorectal cancer (CRC) risk. However, data on the association between HRT and OC and risk of different clinicopathological and molecular subsets of CRC are lacking. The aim of this molecular pathological epidemiology study was therefore to evaluate the associations between HRT and OC use and risk of specific CRC subgroups, overall and by tumour site.METHOD: In the population-based prospective cohort study Mamö Diet and Cancer, including 17035 women, 304 cases of CRC were diagnosed up until 31 December 2008. Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status had previously been assessed in tissue microarrays with tumours from 280 cases. HRT was assessed as current use of combined HRT (CHRT) or unopposed oestrogen (ERT), and analysed among 12583 peri-and postmenopausal women. OC use was assessed as ever vs never use among all women in the cohort. A multivariate Cox regression model was applied to determine hazard ratios for risk of CRC, overall and according to molecular subgroups, in relation to HRT and OC use.RESULTS: There was no significantly reduced risk of CRC by CHRT or ERT use, however a reduced risk of T-stage 1-2 tumours was seen among CHRT users (HR: 0.24; 95% CI: 0.09-0.77).Analysis stratified by tumour location revealed a reduced overall risk of rectal, but not colon, cancer among CHRT and ERT users, including T stage 1-2, lymph node negative, distant metastasis-free, cyclin D1 - and p53 negative tumours.In unadjusted analysis, OC use was significantly associated with a reduced overall risk of CRC (HR: 0.56; 95% CI: 0.44-0.71), but this significance was not retained in adjusted analysis (HR: 1.05: 95% CI: 0.80-1.37). A similar risk reduction was seen for the majority of clinicopathological and molecular subgroups.CONCLUSION: Our findings provide information on the relationship between use of HRT and OC and risk of clinicopathological and molecular subsets of CRC.
43.	Brändstedt, Jenny, et al. (författare) Influence of anthropometric factors on tumour biological characteristics of colorectal cancer in men and women : a cohort study 2013 Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 11 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Obesity is a well established risk factor of colorectal cancer (CRC), but how body size influences risk of colorectal cancer defined by key molecular alterations remains unclear. In this study, we investigated the relationship between height, weight, body mass index (BMI), waist- and hip circumference, waist-hip ratio (WHR) and risk of CRC according to expression of beta-catenin, cyclin D1, p53 and microsatellite instability status of the tumours in men and women, respectively.METHODS: Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status was assessed in tissue microarrays with tumours from 584 cases of incident CRC in the Malmö Diet and Cancer Study. Six anthropometric factors: height, weight, BMI, waist- and hip circumference, and WHR were categorized by quartiles of baseline measurements and relative risks of CRC according to expression of beta-catenin, cyclin D1, p53 and MSI status were calculated using multivariate Cox regression models.RESULTS: High height was associated with risk of cyclin D1 positive, and p53 negative CRC in women but not with any investigative molecular subsets of CRC in men. High weight was associated with beta-catenin positive, cyclin D1 positive, p53 negative and microsatellite stable (MSS) tumours in women, and with beta-catenin negative and p53 positive tumours in men. Increased hip circumference was associated with beta-catenin positive, p53 negative and MSS tumours in women and with beta-catenin negative, cyclin D1 positive, p53 positive and MSS tumours in men. In women, waist circumference and WHR were not associated with any molecular subsets of CRC. In men, both high WHR and high waist circumference were associated with beta-catenin positive, cyclin D1 positive and p53 positive tumours. WHR was also associated with p53 negative CRC, and waist circumference with MSS tumours. High BMI was associated with increased risk of beta-catenin positive and MSS CRC in women, and with beta-catenin positive, cyclin D1 positive and p53 positive tumours in men.CONCLUSIONS: Findings from this large prospective cohort study indicate sex-related differences in the relationship between obesity and CRC risk according to key molecular characteristics, and provide further support of an influence of lifestyle factors on different molecular pathways of colorectal carcinogenesis.
44.	Castellano, Daniel, et al. (författare) The role of RANK-ligand inhibition in cancer : the story of denosumab 2011 Ingår i: The Oncologist. - : Oxford University Press (OUP). - 1549-490X .- 1083-7159. ; 16:2, s. 45-136 Forskningsöversikt (refereegranskat)abstract The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.
45.	Eberhard, Jakob, et al. (författare) A cohort study of the prognostic and treatment predictive value of SATB2 expression in colorectal cancer 2012 Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 106:5, s. 931-938 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Special AT-rich sequence-binding protein 2 (SATB2) is a novel diagnostic marker of colorectal cancer (CRC), and loss of SATB2 has been linked to poor survival from the disease. In this study, we validated the prognostic ability of SATB2 expression in a large, prospective CRC cohort.METHODS: Immunohistochemical SATB2 expression was assessed in 527 incident CRC cases from the Malmö Diet and Cancer Study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB2 expression on cancer-specific survival (CSS) and overall survival (OS).RESULTS: High SATB2 expression was associated with a prolonged CSS in the full cohort (hazard ratio (HR)=0.61; 95% CI 0.41-0.92) and in colon cancer (HR=0.39; 95% CI 0.20-0.75), remaining significant in multivariable analysis of colon cancer (HR=0.49; 95% CI 0.25-0.96), with similar findings for OS. In curatively resected stage III-IV patients, a significant benefit from adjuvant and/or neoadjuvant therapy was observed for SATB2 high tumours (P(interaction)=0.037 for OS) and high SATB2 expression in rectal cancer correlated with an enhanced effect of neoadjuvant therapy (P(interaction)=0.033 for OS).CONCLUSION: High SATB2 expression is an independent marker of good prognosis in colon cancer and may modulate sensitivity to chemotherapy and radiation.
46.	Fristedt, Richard, et al. (författare) Reduced expression of the polymeric immunoglobulin receptor in pancreatic and periampullary adenocarcinoma signifies tumour progression and poor prognosis 2014 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11, s. 112728-112728 Tidskriftsartikel (refereegranskat)abstract The polymeric immunoglobulin receptor (pIgR) is a key component of the mucosal immune system that mediates epithelial transcytosis of immunoglobulins. High pIgR expression has been reported to correlate with a less aggressive tumour phenotype and an improved prognosis in several human cancer types. Here, we examined the expression and prognostic significance of pIgR in pancreatic and periampullary adenocarcinoma. The study cohort encompasses a consecutive series of 175 patients surgically treated with pancreaticoduodenectomy for pancreatic and periampullary adenocarcinoma in Malmö and Lund University Hospitals, Sweden, between 2001-2011. Tissue microarrays were constructed from primary tumours (n = 175) and paired lymph node metastases (n = 105). A multiplied score was calculated from the fraction and intensity of pIgR staining. Classification and regression tree analysis was used to select the prognostic cut-off. Unadjusted and adjusted hazard ratios (HR) for death and recurrence within 5 years were calculated. pIgR expression could be evaluated in 172/175 (98.3%) primary tumours and in 96/105 (91.4%) lymph node metastases. pIgR expression was significantly down-regulated in lymph node metastases as compared with primary tumours (p = 0.018). Low pIgR expression was significantly associated with poor differentiation grade (p < 0.001), perineural growth (p = 0.027), lymphatic invasion (p = 0.016), vascular invasion (p = 0.033) and infiltration of the peripancreatic fat (p = 0.039). In the entire cohort, low pIgR expression was significantly associated with an impaired 5-year survival (HR = 2.99, 95% confidence interval (CI) 1.71-5.25) and early recurrence (HR = 2.89, 95% CI 1.67-4.98). This association remained significant for survival after adjustment for conventional clinicopathological factors, tumour origin and adjuvant treatment (HR = 1.98, 95% CI 1.10-3.57). These results demonstrate, for the first time, that high tumour-specific pIgR expression signifies a more favourable tumour phenotype and that low expression independently predicts a shorter survival in patients with pancreatic and periampullary cancer. The mechanistic basis for the putative tumour suppressing properties of pIgR in these cancers merits further study.
47.	Västermark, Åke, et al. (författare) Polymorphic variation in the androgen receptor gene : association with risk of testicular germ cell cancer and metastatic disease 2011 Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:3, s. 413-419 Tidskriftsartikel (refereegranskat)abstract Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR) gene polymorphisms in relation to the risk, histological type and progression of TGCC was undertaken. In 367 TGCC cases and 214 controls, AR CAG and GGN repeat lengths were determined and 11 haplotype-tagging single nucleotide polymorphisms (SNPs) were genotyped. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated for the risk of TGCC, non-seminoma versus seminoma and metastatic versus localised (stage I) disease. For the non-coding SNP, rs12014709, the minor genotype (G) was found in 10% of the cases and in 5.1% of the controls, conferring an OR of 2.07 (95% CI: 1.03-4.15) for having TGCC. Furthermore, short GGN (<23) was associated with an increased risk of metastatic disease (OR: 2.15; 95% CI: 1.04-4.45). The AR polymorphisms found by us might be involved in gene-environment interaction by increasing the susceptibility to the effect of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between environmental factors and androgen receptor variants in relation to the risk of testicular malignancy.
48.	Walther, Charles, et al. (författare) Cytogenetic and single nucleotide polymorphism array findings in soft tissue tumors in infants 2013 Ingår i: Cancer Genetics. - : Elsevier BV. - 2210-7762. ; 206:7-8, s. 299-303 Tidskriftsartikel (refereegranskat)abstract Soft tissue tumors in children under one year of age (infants) are rare. The etiology is usually unknown, with external factors or congenital birth defects and hereditary syndromes being recognized in only a small proportion of the cases. We ascertained the cytogenetic findings in 16 infants from whom tumor tissue had been obtained during a 25-year period. In eight of them, single nucleotide polymorphism (SNP) array analyses could also be performed. No constitutional chromosome aberrations were detected, and assessment of clinical files did not reveal any congenital or later anatomical defects. Three tumors--one infantile fibrosarcoma, one embryonal rhabdomyosarcoma, and one angiomatoid fibrous histiocytoma (AFH)--had abnormal karyotypes. As the AFH had an exchange between chromosome arms 12p and 15q, additional fluorescence in situ hybridization and reverse transcription-polymerase chain reaction analyses were performed, unexpectedly revealing an ETV6/NTRK3 fusion. Three of the eight tumors, including the AFH with an abnormal karyotype, analyzed by SNP array showed aberrations (loss of heterozygosity or imbalances). The present series suggests that the addition of array-based technologies is valuable for detecting underlying pathogenetic mechanisms.
49.	Wangefjord, Sakarias, et al. (författare) Associations of beta-catenin alterations and MSI screening status with expression of key cell cycle regulating proteins and survival from colorectal cancer 2013 Ingår i: Diagnostic Pathology. - : Springer Science and Business Media LLC. - 1746-1596. ; 8, s. 10-10 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Despite their pivotal roles in colorectal carcinogenesis, the interrelationship and prognostic significance of beta-catenin alterations and microsatellite instability (MSI) in colorectal cancer (CRC) needs to be further clarified. In this paper, we studied the associations between beta-catenin overexpression and MSI status with survival from CRC, and with expression of p21, p27, cyclin D1 and p53, in a large, prospective cohort study.METHODS: Immunohistochemical MSI-screening status and expression of p21, p27 and p53 was assessed in tissue microarrays with tumours from 557 cases of incident CRC in the Malmö Diet and Cancer Study. Chi Square and Spearman's correlation tests were used to explore the associations between beta-catenin expression, MSI status, clinicopathological characteristics and investigative parameters. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between beta-catenin overexpression, MSI status and cancer specific survival (CSS).RESULTS: Positive MSI screening status was significantly associated with older age, female sex, proximal tumour location, non-metastatic disease, and poor differentiation, and inversely associated with beta-catenin overexpression. Beta-catenin overexpression was significantly associated with distal tumour location, low T-stage and well-differentiated tumours. Patients with MSI tumours had a significantly prolonged CSS in the whole cohort, and in stage III-IV disease, also in multivariable analysis, but not in stage I-II disease. Beta-catenin overexpression was associated with a favourable prognosis in the full cohort and in patients with stage III-IV disease. Neither MSI nor beta-catenin status were predictive for response to adjuvant chemotherapy in curatively treated stage III patients. P53 and p27 expression was positively associated with beta-catenin overexpression and inversely associated with MSI. Cyclin D1 expression was positively associated with MSI and beta-catenin overexpression, and p21 expression was positively associated with MSI but not beta-catenin overexpression.CONCLUSIONS: Findings from this large, prospective cohort study demonstrate that MSI screening status in colorectal cancer is an independent prognostic factor, but not in localized disease, and does not predict response to adjuvant chemotherapy. Beta-catenin overexpression was also associated with favourable outcome but not a treatment predictive factor. Associations of MSI and beta-catenin alterations with other investigative and clinicopathological factors were in line with the expected.VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8778585058652609.
50.	Zinsky, R., et al. (författare) News from the underground: What were the most important scientific/clinical take-home messages for juniors? 2014 Ingår i: Breathe. - : European Respiratory Society. - 1810-6838 .- 2073-4735. ; 10:4, s. 333-335 Tidskriftsartikel (refereegranskat)

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