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| 2. |
- Hau, Sofie Olsson, et al.
(author)
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Chemotherapy, host response and molecular dynamics in periampullary cancer : The CHAMP study
- 2020
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the "Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)" study aims to monitor these processes to gain new insight into this perplexing disease. Methods: The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion: Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration: This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.
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| 3. |
- Wahlin, Sara, et al.
(author)
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Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer : a comparative study of transurethral resection and cystectomy specimens
- 2019
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In: OncoImmunology. - 2162-4011. ; 8:11
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Journal article (peer-reviewed)abstract
- In patients with muscle invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) prior to radical cystectomy has improved survival but there is an urgent unmet need to identify prognostic and predictive biomarkers to stratify patients who will benefit from treatment. This study aimed to examine the composition of tumor-infiltrating immune cells in MIBC, with particular reference to the clinical outcome and the potential modifying effect of NAC. To this end, the expression of CD8+ and FoxP3+ T cells, CD20+ B cells, PD-1+ and PD-L1+ immune cells and PD-L1+ tumor cells was evaluated by immunohistochemistry on tissue microarrays with paired transurethral resection (TURB) specimens, cystectomy specimens and lymph node metastases from 145 patients, 65 of whom had received NAC. Kaplan–Meier and Cox regression analyses were applied to assess the impact of investigated cell subsets on time to recurrence (TTR). In cystectomy specimens, high infiltration of the investigated immune cell populations, but not PD-L1+ tumor cells, were independently associated with a prolonged TTR, whereas in TURB specimens, this association was only seen for CD8+ lymphocytes. An additive beneficial prognostic effect of NAC was seen for the majority of the cell subsets but there was no significant interaction between any immune marker and NAC in relation to TTR. Furthermore, no differences in cell densities prior to NAC treatment were observed between complete and non-complete responders, or pre- and posttreatment in non-complete responders. In conclusion, immune cell infiltration provides important prognostic information in both pre- and postsurgical samples of MIBC, independently of NAC.
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| 4. |
- Albin, Maria, et al.
(author)
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0253 Hairdressers are occupationally exposed to ortho- and meta- toluidine
- 2014
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In: Occupational and Environmental Medicine. - : BMJ. - 1470-7926 .- 1351-0711. ; 71 Suppl 1, s. 32-33
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Conference paper (peer-reviewed)abstract
- Hairdressing work is classified as carcinogenic based on excess risk for bladder cancer. We aimed at evaluating if current hairdressers are exposed to established/suspected bladder carcinogens (aromatic amines) and indicate possible sources of exposure.
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| 5. |
- Alvehus, Malin, et al.
(author)
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Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training
- 2014
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In: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 114:7, s. 1463-1471
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Journal article (peer-reviewed)abstract
- The effects of resistance training on mitochondrial biogenesis and oxidative capacity in skeletal muscle are not fully characterized, and even less is known about alterations in adipose tissue. We aimed to investigate adaptations in oxidative metabolism in skeletal muscle and adipose tissue after 8 weeks of heavy resistance training in apparently healthy young men. Expression of genes linked to oxidative metabolism in the skeletal muscle and adipose tissue was assessed before and after the training program. Body composition, peak oxygen uptake (VO2 peak), fat oxidation, activity of mitochondrial enzyme in muscle, and serum adiponectin levels were also determined before and after resistance training. In muscle, the expression of the genes AdipoR1 and COX4 increased after resistance training (9 and 13 %, respectively), whereas the expression levels of the genes PGC-1 alpha, SIRT1, TFAM, CPT1b, and FNDC5 did not change. In adipose tissue, the expression of the genes SIRT1 and CPT1b decreased after training (20 and 23 %, respectively). There was an increase in lean mass (from 59.7 +/- A 6.1 to 61.9 +/- A 6.2 kg), VO2 peak (from 49.7 +/- A 5.5 to 56.3 +/- A 5.0 ml/kg/min), and fat oxidation (from 6.8 +/- A 2.1 to 9.1 +/- A 2.7 mg/kg fat-free mass/min) after training, whereas serum adiponectin levels decreased significantly and enzyme activity of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase did not change. Despite significant increases in VO2 peak, fat oxidation, and lean mass following resistance training, the total effect on gene expression and enzyme activity linked to oxidative metabolism was moderate.
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| 6. |
- Andersson, Gustav, et al.
(author)
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Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival : validatory study of two independent patient cohorts
- 2014
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In: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 14:1, s. 36-
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Journal article (peer-reviewed)abstract
- Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
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| 7. |
- Andersson, Nina, et al.
(author)
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Lymphocyte antigen 6 superfamily member D is a marker of urothelial and squamous differentiation : Implications for risk stratification of bladder cancer
- 2020
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In: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 8:1
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Journal article (peer-reviewed)abstract
- Background: Screening across a multitude of normal and malignant tissues revealed an enhanced expression of lymphocyte antigen 6 superfamily member D (LY6D) in squamous epithelium and urothelium, as well as in malignancies derived therefrom. The aim of this study was to further delineate the protein expression of LY6D in urothelial bladder cancer, with particular attention to its relationship with clinicopathological characteristics and patient outcome. Methods: Immunohistochemical expression of LY6D was assessed in tissue microarrays with urothelial bladder cancer tumours from three independent patient cohorts; one with transurethral resection of the bladder (TURB) specimens of mixed tumour stages from 110 consecutive cases, one with tumours of mixed stages from 260 incident cases in a population-based cohort, and one with paired TURB specimens, resected tumours and a subset of lymph node metastases from 145 patients with muscle-invasive bladder cancer (MIBC). Chi-square and non-parametric tests were applied to examine associations of LY6D expression with clinicopathological characteristics. Kaplan-Meier and Cox regression analyses were applied to examine 5-year overall survival (OS) and recurrence free survival (RFS) in relation to LY6D expression. Results: In the two cohorts with mixed stages, positive LY6D expression was denoted in 63 and 64% of the cases, respectively, and found to be significantly higher in low-grade and less invasive tumours. Negative LY6D expression was significantly associated with a reduced 5-year OS, although not independently of established prognostic factors. In the population-based cohort, LY6D expression was higher in tumours with squamous differentiation and lower in other variant histologies compared to pure urothelial tumours, and the association of LY6D expression with survival was somewhat enhanced after exclusion of the former. LY6D expression was generally lower in the MIBC cohort, and even more reduced in resected tumours compared to TURB specimens in patients who had not received neoadjuvant chemotherapy. There were no significant associations between LY6D expression and RFS, neither allover nor in relation to neoadjuvant chemotherapy. Conclusion: LY6D is a marker of urothelial and squamous differentiation that may add useful diagnostic and prognostic information to better guide the clinical management of bladder cancer, given that the presence of variant histology is taken into account.
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| 8. |
- Andersson, Patrik, 1974, et al.
(author)
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Framtidsbilder för samhällsbyggnad
- 2006
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Reports (other academic/artistic)abstract
- Framtidsbilder för samhällsbyggnad 2020De kommande 15 åren står institutionen för Bygg- och miljöteknik inför stora förändringar. Därför har institutionen initierat projektet Framtidsbilder 2020 där man engagerat en framtidspanel bestående av elva yngre disputerade forskare. Arbetet inleddes med ett breddgruppsmöte där 110 personer representerande institutionens personal och studenter deltog. Vid mötet identifierades ett antal trender och osäkra utvecklingar som påverkar framtiden inom samhällsbyggnadsområdet. Deltagarna bidrog också med idéer till en önskvärd utveckling, vilket har sammanställts och utgör grunden till en gemensam önskvärd framtid/vision för institutionen. Materialet från breddgruppsmötet har bearbetats av Framtidspanelen och resulterat i fyra scenarier som beskriver hur samhällsbyggnadsområdet kan se ut år 2020. Syftet med framtidsbilderna är att de ska vara vägledande för institutionens beslut och förhållningssätt under de kommande åren.Fyra scenarierTurning TorsoSamhället präglas av en ekonomi som är på uppgång, och av ett nytänkande och öppet samhälle. Materiell status och individualism är viktigt. Detta leder till en hög arbetsbelastning samt krav på exklusiva varor av hög kvali-tet. Det finns en stor medvetenhet om miljöpåverkan och klimatförändringar och lösningarna för att klara energiförsörjningen är innovativa.Eco-metropolenDet sveper en grön våg genom dagens samhälle. Under de senaste 15 åren har vi insett att jorden skall vara en bebolig plats även åt dem som kommer efter oss. Vi söker ständigt efter nya, mer förfinade metoder att tillvarata de resurser vi har. Samhället och individen är i balans. Ekonomin är god och vi är miljömedvetna, trygga och integrerade. Nytänkande premieras och icke- materialistiska värderingar står högt i kurs. Vi tänker individuellt, men agerar mer än gärna för kollektivets bästa. Utbildning är gratis TrädgårdsstadenEtt samhälle där vi lärt oss hantera stress, men känner oss otrygga och helst umgås i slutna sociala sammanhang. Vi bor enkelt inne i stan, eller gärna på landsbygden nära storstäderna. Minskade behov av högutbildade i samhället gör att vi har svårt att rekrytera studenter till teknikutbildningar. Det traditionella tankesättet leder till kulturkrockar med företag och personer från andra länder.Gated communitiesFörsämrad ekonomi och ökad egoism har lett fram till ett stressat, otryggt och segregerat samhälle. Accelererande klimatförändringar och ökad miljö-påverkan skrämmer oss, men trots det åtgärdar vi inte problemen, utan koncentrerar oss på konsekvenserna. Arbetslöshet i samhällsbyggnadssek-torn leder till sänkt status för samhällsbyggaren. Vi har därför svårt att rekrytera studenter, och även forskningen har låg status.
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| 9. |
- Arne, Mats, 1954-, et al.
(author)
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How often is diagnosis of COPD confirmed with spirometry?
- 2010
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In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 104:4, s. 550-556
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Journal article (peer-reviewed)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality worldwide. Diagnosis is customarily confirmed with spirometry, but there are few studies on documented spirometry use in everyday clinical practice. Methods: In a cross-sectional survey and study of the medical records of primary and secondary care COPD patients aged 18-75 in a Swedish region, patients with COPD were randomly selected from the registers of 56 primary care centres and 14 hospital outpatient clinics. Spirometry data at diagnosis ±6 months were analyzed. Results: From 1,114 patients with COPD, 533 with a new diagnosis of COPD during the four-year study period were identified. In 59% (n=316), spirometry data in connection with diagnosis were found in the medical records. Spirometry data with post-bronchodilator forced expiratory volume in one second (FEV1)/ vital capacity (VC) ratios were available in 45% (n=241). FEV1/VC ratio <0.70 were found in 160 patients, which corresponds to 30% of the patients with a new diagnosis. Lower age, female gender, current smoking, higher body mass index (BMI) and shorter forced exhalation time were related to COPD diagnosis despite an FEV1/VC ratio of ≥0.70. The most common problem in the quality assessment was an insufficient exhalation time. Conclusions: Only a third of Swedish patients with COPD had their diagnosis confirmed with spirometry. Our data indicate that female gender, current smoking, higher BMI and short exhalation time increase the risk of being diagnosed with COPD without fulfilling the spirometric criteria for the disease.
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| 10. |
- Bernhardsson, Susanne, 1958, et al.
(author)
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Implementation of physical activity on prescription for children with obesity in paediatric health care (IMPA): protocol for a feasibility and evaluation study using quantitative and qualitative methods
- 2022
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In: Pilot and Feasibility Studies. - : Springer Science and Business Media LLC. - 2055-5784. ; 8:1
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Journal article (peer-reviewed)abstract
- Background: Physical inactivity is a main cause of childhood obesity which tracks into adulthood obesity, making it important to address early in life. Physical activity on prescription (PAP) is an evidence-based intervention that has shown good effect on physical activity levels in adults, but has not been evaluated in children with obesity. This project aims to evaluate the prerequisites, determinants, and feasibility of implementing PAP adapted to children with obesity and to explore children's, parents', and healthcare providers' experiences of PAP. Methods: In the first phase of the project, healthcare providers and managers from 26 paediatric clinics in Region Vastra Gotaland, Sweden, will be invited to participate in a web-based survey and a subset of this sample for a focus group study. Findings from these two data collections will form the basis for adaptation of PAP to the target group and context. In a second phase, this adapted PAP intervention will be evaluated in a clinical study in a sample of approximately 60 children with obesity (ISO-BMI > 30) between 6 and 12 years of age and one of their parents/legal guardians. Implementation process and clinical outcomes will be assessed pre- and post-intervention and at 8 and 12 months' follow-up. Implementation outcomes are the four core constructs of the Normalization Process Theory; coherence, cognitive participation, collective action, and reflexive monitoring; and appropriateness, acceptability, and feasibility of the PAP intervention. Additional implementation process outcomes are recruitment and attrition rates, intervention fidelity, dose, and adherence. Clinical outcomes are physical activity pattern, BMI, metabolic risk factors, health-related quality of life, sleep, and self-efficacy and motivation for physical activity. Lastly, we will explore the perspectives of children and parents in semi-structured interviews. Design and analysis of the included studies are guided by the Normalization Process Theory. Discussion: This project will provide new knowledge regarding the feasibility of PAP for children with obesity and about whether and how an evidence-based intervention can be fitted and adapted to new contexts and populations. The results may inform a larger scale trial and future implementation and may enhance the role of PAP in the management of obesity in paediatric health care in Sweden.
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