| 31. |
- Näppä, Ulla, et al.
(author)
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The effect of bereavement groups on grief, anxiety, and depression - a controlled, prospective intervention study
- 2016
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In: BMC Palliative Care. - : Springer Science and Business Media LLC. - 1472-684X. ; 15
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Journal article (peer-reviewed)abstract
- Background: Bereavement groups are believed to be beneficial as preventive interventions to reduce the development of complicated grief for people at risk after the death of a significant other. This study aimed to investigate whether measurable effects on grief, anxiety, and depression could be detected in those participating in bereavement groups compared to non-participating controls.Methods: Questionnaires covering the Texas Revised Inventory of Grief (TRIG), the Hospital Anxiety and Depression Scale (HADS), and background questions were handed out pre-intervention, five weeks and one year post-intervention to bereaved caregivers invited to bereavement groups. The results were analysed with non-parametric methods.Results: A total of 124 individuals answered the questionnaires, and were divided into three categories: participants, non-participants unable to participate, and non-participants not wanting to participate in bereavement groups. At the one-year follow up, participants and those unable to participate reported higher levels of grief and were more anxious than those not wanting to participate. Depression did not differ between the groups.Conclusions: Participation in bereavement groups did not produce any effects on grief, anxiety, or depression in comparison to non-participants who were unable to participate. Non-participants who did not want to participate reported lower levels of grief and anxiety than the other two groups.
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| 32. |
- Sandén, Emma, et al.
(author)
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Preoperative systemic levels of VEGFA, IL-7, IL-17A, and TNF-beta delineate two distinct groups of children with brain tumors
- 2016
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In: Pediatr Blood Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:12, s. 2112-2122
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Journal article (peer-reviewed)abstract
- BackgroundPrimary brain tumors are the most common solid tumors in children. Increasing evidence demonstrates diverse intratumoral immune signatures, which are tentatively reflected in peripheral blood. ProcedureTwenty cytokines were analyzed in preoperative plasma samples from five healthy children and 45 children with brain tumors, using a multiplex platform (MesoScale Discovery V-PLEX (R)). Tumor types included medulloblastoma (MB), ependymoma, sarcoma, high-grade glioma, pilocytic astrocytoma, and other low-grade gliomas. ResultsA panel of four cytokines [VEGFA, interleukin (IL)-7, IL-17A, and tumor necrosis factor (TNF)-] delineated two distinct patient groups, identified as VEGFA(high)IL-7(high)IL-17A(low)TNF-(low) (Group A) and VEGFA(low)IL-7(low)IL-17A(high)TNF-(high) (Group B). Healthy controls and the vast majority of patients with MB were found within Group A, whereas patients with other tumor types were equally distributed between the two groups. Unrelated to A/B affiliation, we detected trends toward increased IL-10 and decreased IL-12/23 and TNF- in several tumor types. Finally, a small number of patients displayed evidence of enhanced systemic immune activation, including elevated levels of interferon-, granulocyte monocyte colony-stimulating factor, IL-6, IL-12/23, and TNF-. Following tumor resection, cytokine levels in a MB patient approached the levels of healthy controls. ConclusionsWe identify common features and individual differences in the systemic immune profiles of children with brain tumors. Overall, patients with MB displayed a uniform cytokine profile, whereas other tumor diagnoses did not predict systemic immunological status in single patients. Future characterization and monitoring of systemic immune responses in children with brain tumors will have important implications for the development and implementation of immunotherapy.
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| 33. |
- Svedberg, Petra, 1973-, et al.
(author)
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Support from healthcare services during transition to adulthood – Experiences of young adult survivors of pediatric cancer
- 2016
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In: European Journal of Oncology Nursing. - London : Elsevier. - 1462-3889 .- 1532-2122. ; 21, s. 105-112
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Journal article (peer-reviewed)abstract
- Purpose: Improved survival rates of pediatric cancer have drawn attention on how to best facilitate long-term follow up and transition from pediatric to adult care. The transition process is multifactorial and necessitates the joint involvement of the patient, the family and the healthcare providers. The purpose of this study was to explore the experiences of support from healthcare services during the transition from adolescence to adulthood described by young adult survivors of pediatric cancer.Methods: A mixed method with a convergent parallel design was used to evaluate the experiences of receiving support from healthcare services (eg pediatric oncology and pediatric clinic) during transition from adolescence to adulthood described by young adult survivors of pediatric cancer (n = 213) in a nation wide cross-sectional survey.Results: A quantitative assessment of the experienced extent and satisfaction of support from healthcare services to handle physical, mental and social changes to continue life after the disease showed that a majority of the participants had received insufficient support. The qualitative analysis indicated a need for equal roles in healthcare to promote participation, a need to manage and process consequences of the disease, and a need for continuous support.Conclusions: During transition to adulthood, there's a need for a personalized care plan that takes a holistic approach towards supporting the young cancer survivor in managing life in the best way. Identifying and handling the individual needs of pediatric cancer survivors is important for providing the resources and support required to increase the likelihood of successful transition to adulthood. © 2016 Elsevier Ltd.
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| 34. |
- Vilhelmsson Timmermand, Oskar, et al.
(author)
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High resolution digital autoradiographic and dosimetric analysis of heterogeneous radioactivity distribution in xenografted prostate tumors
- 2016
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In: Medical Physics. - : Wiley. - 0094-2405. ; 43:12, s. 6632-6643
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Journal article (peer-reviewed)abstract
- The first main aim of this study was to illustrate the absorbed dose rate distribution from 177Lu in sections of xenografted prostate cancer (PCa) tumors using high resolution digital autoradiography (DAR) and compare it with hypothetical identical radioactivity distributions of 90Y or 7 MeV alpha-particles. Three dosimetry models based on either dose point kernels or Monte Carlo simulations were used and evaluated. The second and overlapping aim, was to perform DAR imaging and dosimetric analysis of the distribution of radioactivity, and hence the absorbed dose rate, in tumor sections at an early time point after injection during radioimmunotherapy using 177Lu-h11B6, directed against the human kallikrein 2 antigen.
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| 35. |
- Lövgren, Malin, et al.
(author)
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Siblings' experiences of their brother's or sister's cancer death : a nationwide follow-up 2-9 years later
- 2016
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In: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 25:4, s. 435-440
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Journal article (peer-reviewed)abstract
- ObjectiveThe aim of this study was to examine siblings' experiences of their brother's or sister's cancer death and if these experiences influenced levels of anxiety 2–9 years later.MethodsThis nationwide survey was conducted in Sweden in 2009. All siblings who had a brother/sister who was diagnosed with cancer before the age of 17 years and who died before the age of 25 years during 2000–2007 were invited. Of those, 174 siblings participated (participation rate: 73%). Mixed data from the survey about the siblings' experiences of death were included as well as data from the Hospital Anxiety and Depression Scale. To examine the experiences, descriptive statistics and content analysis were used. Mann–Whitney U-test was conducted to investigate if the experiences influenced anxiety 2–9 years later.ResultsThe siblings reported poor knowledge and experienced a lack of communication about their brother's/sister's death, for example, about the time frame, bodily changes near death, and about their own experiences. Siblings who reported that no one talked with them about what to expect when their brother/sister was going to die reported higher levels of anxiety 2–9 years after the loss. Seventy percent reported that they witnessed their brother/sister suffering in the last hours in life. Many of those who were not present during the illness period and at the time of death expressed regret.ConclusionIt is important to prepare siblings for their brother's/sister's illness and death as it may decrease anxiety and regrets later on
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| 36. |
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| 37. |
- Assi, N., et al.
(author)
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A treelet transform analysis to relate nutrient patterns to the risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2016
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In: Public Health Nutrition. - 1368-9800 .- 1475-2727. ; 19:2, s. 242-254
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Journal article (peer-reviewed)abstract
- Copyright © The Authors 2015 Objective: Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology. Design: Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison. Setting: The European Prospective Investigation into Cancer and Nutrition (EPIC). Subjects: Women (n 334 850) from the EPIC study. Results: The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, P trend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, P trend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, P trend<0·01). Conclusions: TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
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| 38. |
- Berglund, U. W., et al.
(author)
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Validation and development of MTH1 inhibitors for treatment of cancer
- 2016
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In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
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Journal article (peer-reviewed)abstract
- Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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| 39. |
- Kling, Teresia, 1985, et al.
(author)
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Integrative Modeling Reveals Annexin A2-mediated Epigenetic Control of Mesenchymal Glioblastoma
- 2016
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In: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 12, s. 72-85
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Journal article (peer-reviewed)abstract
- Glioblastomas are characterized by transcriptionally distinct subtypes, but despite possible clinical relevance, their regulation remains poorly understood. The commonly used molecular classification systems for GBM all identify a subtype with high expression of mesenchymal marker transcripts, strongly associated with invasive growth. We used a comprehensive data-driven network modeling technique (augmented sparse inverse covariance selection, aSICS) to define separate genomic, epigenetic, and transcriptional regulators of glioblastoma subtypes. Our model identified Annexin A2 (ANXA2) as a novel methylation-controlled positive regulator of the mesenchymal subtype. Subsequent evaluation in two independent cohorts established ANXA2 expression as a prognostic factor that is dependent on ANXA2 promoter methylation. ANXA2 knockdown in primary glioblastoma stem cell-like cultures suppressed known mesenchymal master regulators, and abrogated cell proliferation and invasion. Our results place ANXA2 at the apex of a regulatory cascade that determines glioblastoma mesenchymal transformation and validate aSICS as a general methodology to uncover regulators of cancer subtypes. (C) 2016 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 40. |
- Bjartell, Anders, et al.
(author)
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Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort
- 2016
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In: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 50:4, s. 255-259
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Journal article (peer-reviewed)abstract
- Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram
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