| 51. |
- Ardenfors, Oscar, et al.
(författare)
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Are IMRT treatments in the head and neck region increasing the risk of secondary cancers?
- 2014
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:8, s. 1041-1047
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Tidskriftsartikel (refereegranskat)abstract
- Background. Intensity-modulated radiation therapy (IMRT) has been increasingly employed for treating head and neck (H&N) tumours due to its ability to produce isodoses suitable for the complex anatomy of the region. The aim of this study was to assess possible differences between IMRT and conformal radiation therapy (CRT) with regard to risk of radiation-induced secondary malignancies for H&N tumours. Material and methods. IMRT and CRT plans were made for 10 H&N adult patients and the resulting treatment planning data were used to calculate the risk of radiation-induced malignancies in four different tissues. Three risk models with biologically relevant parameters were used for calculations. The influence of scatter radiation and repeated imaging sessions has also been investigated. Results. The results showed that the total lifetime risks of developing radiation-induced secondary malignancies from the two treatment techniques, CRT and IMRT, were comparable and in the interval 0.9-2.5%. The risk contributions from the primary beam and scatter radiation were comparable, whereas the contribution from repeated diagnostic imaging was considerably smaller. Conclusion. The results indicated that the redistribution of the dose characteristic to IMRT leads to a redistribution of the risks in individual tissues. However, the total levels of risk were similar between the two irradiation techniques considered.
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| 52. |
- Rosell, Johan, et al.
(författare)
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Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer : results from a randomized trial with long term follow-up
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUNDTamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.METHODSOur study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).RESULTSIn the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.CONCLUSIONSIn this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.
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| 53. |
- Ryk, C., et al.
(författare)
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The (CCTTT)n microsatellite polymorphism in the NOS2 gene may influence lung cancer risk and long-term survival, especially in non-smokers
- 2014
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Ingår i: Tumor Biology. - : Kluwer Academic Publishers. - 1010-4283 .- 1423-0380. ; 35:5, s. 4425-4434
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed the associations of the NOS2 (CCTTT)n promoter polymorphism to lung cancer risk and tumor histology in smokers and non-smokers. We also investigated lung cancer long-term survival in relation to the polymorphism, smoking data, histology, age at diagnosis, and gender. One hundred eighty-five lung-cancer patients and 164 matched controls, where non-smokers were enriched among the lung cancer cases, were genotyped by fragment analysis and sequencing. Genotypes were combined with information on histology, patient smoking status, and cancer-specific death, using a 20-year follow-up. We divided the (CCTTT)n alleles into short (n≤10), intermediate (n=11-12), and long (n≥13). Patients homozygous for short repeats had significantly increased risk of lung cancer (p=0.030) compared to carriers of two long alleles (LL). Lack of long allele was associated with a significantly increased lung cancer risk overall (p=0.011), especially among non-smokers (p=0.001). A significantly higher lung cancer survival was seen in non-smokers compared to smokers (p=0.046) and in low-dose smokers compared to high-dose smokers at the time of diagnosis (p=0.028). Moreover, non-smoking patients with squamous cell carcinoma (p=0.015) or adenocarcinoma (p=0.024) showed a significantly lower survival compared to other lung carcinomas. Nitric oxide can induce proliferation as well as apoptosis depending on cellular context. Our results suggest that the (CCTTT)n NOS2 microsatellite may influence the risk of developing lung cancer, especially in non-smokers, possibly by affecting intracellular nitric oxide levels. Our results also give additional information about the yet poorly understood etiological and prognostic differences between lung cancer in non-smokers and smokers. © International Society of Oncology and BioMarkers (ISOBM) 2014.
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| 54. |
- Cernvall, Martin, 1980-
(författare)
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Symptoms of Posttraumatic Stress in Parents of Children on Cancer Treatment : Factor Structure, Experiential Avoidance, and Internet-based Guided Self-help
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Having a child diagnosed with cancer is stressful and many parents of children on treatment for cancer report symptoms of posttraumatic stress (PTSS). The overall purpose was to, among parents of children on treatment for cancer, investigate the factor structure of PTSS; investigate the relationships between experiential avoidance (EA), rumination, PTSS and depression; and to develop, test, and evaluate a guided self-help intervention provided via the internet.In a longitudinal study with three assessments (n = 249-203) results indicated that a four-factor solution of PTSS including the factors re-experiencing, avoidance, dysphoria, and hyper-arousal provided best fit and that the pattern and size of factor loadings were equivalent across the three assessments (Study I). In a case study with pre-, post-, and follow-up assessments a guided self-intervention was well received with clinical significant and reliable improvements in PTSS, depression, and quality of life (Study II). Furthermore, in cross-sectional analyses (n = 79) EA and rumination were positively associated with PTSS and depression and provided incremental explanation in depression while controlling for demographic characteristics, anxiety, and PTSS. In longitudinal analyses (n = 20), EA but not rumination predicted PTSS and depression while controlling for initial levels (Study III). Finally, in a randomized controlled trial with parents fulfilling the modified symptom criteria on the PTSD-Checklist allocated to guided self-help via the internet (n = 31) or to a wait-list control condition (n = 27) there was a significant intervention effect with a large effect size for the primary outcome PTSS. Similar results were observed for the secondary outcomes depression and anxiety, but not for EA and rumination. Exploratory analyses suggested that the relationships between EA and PTSS and between EA and depression were weakened in the intervention group (Study IV).The studies included in the current thesis suggest that a four-factor solution should be used when assessing PTSS in parents of children on cancer treatment. Furthermore, rumination and EA in particular seem to be important constructs to consider when understanding PTSS and depression in this population. Finally, guided self-help via the internet shows promise in reducing PTSS and depression among parents of children on cancer treatment who report a high level of PTSS.
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| 55. |
- Saboonchi, Fredrik, et al.
(författare)
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Changes in caseness of anxiety and depression in breast cancer patients during the first year following surgery : patterns of transiency and severity of the distress response
- 2014
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1462-3889 .- 1532-2122. ; 18:6, s. 598-604
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychological distress is prevalent in patients with breast cancer and is viewed as a non-pathological occurrence. Severe distress and mental disorder display a substantial overlap in both conceptual contexts and studies in oncological settings. A domain that may contribute to distinguishing non-pathological distress from signs of potential disorder is the transiency of distress.AIM: To examine the transiency of distress response in breast cancer patients by investigating the changes in clinical caseness of depression and anxiety during one year following surgery.METHODS: Data on the Hospital Anxiety and Depression Scale from a cohort of 715 women with breast cancer on three assessments within one year following breast surgery were subjected to Generalized Estimation Equation Analysis, McNemar's test, and logistic regression.RESULTS: There was a significant decrease in the proportions of anxiety cases from baseline (37.7%) to 4 months (26.7%) but no significant change from 4 to 12 months. Caseness in depression significantly increased from baseline (18.5%) to 4 months (21.5%) but decreased to 15.3% at 12 months. Only experience of major adverse life events contributed to 12 months caseness of anxiety and depression beyond baseline caseness.DISCUSSION: The average decrease in caseness of anxiety and depression a year following surgery lends support to the view of distress as a transient non-pathological response. A subgroup of patients, however, displayed enduring or recurrent severe distress indicating the presence of potential disorder. The findings emphasize the importance of screening and follow up monitoring of distress.
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| 56. |
- Teras, Lauren R., et al.
(författare)
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Body size and multiple myeloma mortality : a pooled analysis of 20 prospective studies
- 2014
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Ingår i: British Journal of Haematology. - : WILEY-BLACKWELL. - 0007-1048 .- 1365-2141. ; 166:5, s. 667-676
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Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a rare but highly fatal malignancy. High body weight is associated with this cancer, but several questions remain regarding the aetiological relevance of timing and location of body weight. To address these questions, we conducted a pooled analysis of MM mortality using 1.5 million participants (including 1388 MM deaths) from 20 prospective cohorts in the National Cancer Institute Cohort Consortium. Proportional hazards regression was used to calculate pooled multivariate hazard ratios (HRs) and 95% confidence intervals (CIs). Associations with elevated MM mortality were observed for higher early-adult body mass index (BMI; HR = 1.22, 95% CI: 1.09-1.35 per 5 kg/m(2)) and for higher cohort-entry BMI (HR 1.09, 95% CI: 1.03-1.16 per 5 kg/m(2)) and waist circumference (HR = 1.06, 95% CI: 1.02-1.10 per 5 cm). In analyses of the joint effect of young adult and baseline BMI, women who were the heaviest, both in early adulthood (BMI 25+) and at cohort entry (BMI 30+) were at greater risk compared to those with BMI 18.5 = 25 at both time points (HR = 1.95, 95% CI: 1.33-2.86) but there was no significant association in men. Waist-to-hip ratio and height were not associated with MM mortality. These observations suggest that overall, and possibly also central, obesity influence myeloma mortality, and women have the highest risk of death from this cancer if they remain heavy throughout adulthood.
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| 57. |
- Hui, Xiao, et al.
(författare)
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Mast cell exosomes promote lung adenocarcinoma cell proliferation - role of KIT-stem cell factor signaling
- 2014
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Ingår i: Cell Communication and Signaling. - 1478-811X. ; 12:64
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Tidskriftsartikel (refereegranskat)abstract
- Background Human cells release nano-sized vesicles called exosomes, containing mRNA, miRNA and specific proteins. Exosomes from one cell can be taken up by another cell, which is a recently discovered cell-to-cell communication mechanism. Also, exosomes can be taken up by different types of cancer cells, but the potential functional effects of mast cell exosomes on tumor cells remain unknown. Methods and results Exosomes were isolated from the human mast cell line, HMC-1, and uptake of PKH67-labelled exosomes by the lung epithelial cell line, A549, was examined using flow cytometry and fluorescence microscopy. The RNA cargo of the exosomes was analyzed with a Bioanalyzer and absence or presence of the c-KIT mRNA was determined by RT-PCR. The cell proliferation was determined in a BrdU incorporation assay, and proteins in the KIT-SCF signaling pathway were detected by Western blot. Our result demonstrates that exosomes from mast cells can be taken up by lung cancer cells. Furthermore, HMC-1 exosomes contain and transfer KIT protein, but not the c-KIT mRNA to A549 cells and subsequently activate KIT-SCF signal transduction, which increase cyclin D1 expression and accelerate the proliferation in the human lung adenocarcinoma cells. Conclusions Our results indicate that exosomes can transfer KIT as a protein to tumor cells, which can affect recipient cell signaling events through receptor-ligand interactions.
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| 58. |
- Jonsson, L., et al.
(författare)
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High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death
- 2014
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Ingår i: Biomarker Research. - : BioMed Central Ltd.. - 2050-7771. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma.Material and methods: Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett's esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS).Results: RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS).Conclusion: High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation.
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| 59. |
- Stjernström, Annika, et al.
(författare)
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Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung
- 2014
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 3:2, s. 337-348
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate how alterations in the PI3K pathway correlate with non-small cell lung cancer subtypes squamous cell carcinoma (SSC) and adenocarcinoma (ADCA). We analyzed copy number variation and protein expression of INPP4B, protein expression of pAkt, PDPK1, and PTEN and mutational status of PIK3CA and PTEN in 180 cases. Nineteen% displayed loss of INPP4B copy, whereas 47% lacked expression, both showing correlation with SCC. Elevated pAkt expression was seen in 63% of all cases, also correlating to SCC. PDPK1 was expressed in 70%, more in male than female patients. Regarding PTEN, 50% displayed loss of expression, of which seven were identified with mutations in the phosphatase domain. We detected nine cases (5%) of PIK3CA mutations, all identified as the E545K hot spot mutation in the helical domain, all except one in SCC. When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA. Interestingly, we also found a strong correlation between high pAkt expression and PTEN expression. As comparison, we also analyzed mitogen-activated protein kinase (MAPK) pathway genes, where we identified fifteen KRAS mutations (8%) and one BRAF mutation (1%), significantly associated to ADCA. No association was found to the Gly972Arg polymorphism of IRS-1, involved in activation of both PI3K and MAPK pathways. In conclusion, we show here that several components of the PI3K pathway, alone and in combination, are correlated to development of SCC of the lung.
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| 60. |
- Porserud, Andrea, et al.
(författare)
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The effects of a physical exercise programme after radical cystectomy for urinary bladder cancer. A pilot randomized controlled trial.
- 2014
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Ingår i: Clinical Rehabilitation. - : Sage Publications. - 0269-2155 .- 1477-0873. ; 28:5, s. 451-459
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Assessment of feasibility and effects of an exercise training programme in patients following cystectomy due to urinary bladder cancer.Design: Single-blind, pilot, randomized controlled trial.Setting:University hospital, Sweden.Subjects: Eighteen patients (64-78 years), of 89 suitable, cystectomized due to urinary bladder cancer, were randomized after hospital discharge to intervention or control.Interventions: The 12-week exercise programme included group exercise training twice a week and daily walks. The control group received only standardized information at discharge.Main outcome measures: Trial eligibility and compliance to inclusion were registered. Assessments of functional capacity, balance, lower body strength and health-related quality of life (HRQoL) with SF-36.Results: Out of 122 patients 89 were eligible, but 64 did not want to participate/were not invited. Twenty-five patients were included, but 7 dropped out before randomization. Eighteen patients were randomized to intervention or control. Thirteen patients completed the training period. The intervention group increased walking distance more than the control group, 109 m (75-177) compared to 62 m (36-119) (P = 0.013), and role physical domain in SF-36 more than the control group (P = 0.031). Ten patients were evaluated one year postoperatively. The intervention group had continued increasing walking distance, 20 m (19-36), whereas the control group had shortened the distance -15.5 m (-43 to -5) (P = 0.010).Conclusions: A 12-week group exercise training programme was not feasible for most cystectomy patients. However, functional capacity and the role-physical domain in HRQoL increased in the short and long term for patients in the intervention group compared with controls.
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