| 11. |
- Riva, Roberto, et al.
(författare)
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Patterns of psychological responses in parents of children that underwent stem cell transplantation
- 2014
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Ingår i: Psycho-Oncology. - : Wiley. - 1057-9249 .- 1099-1611. ; 23:11, s. 1307-1313
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveHematopoietic stem cell transplantation (HSCT) is curative in several life-threatening pediatric diseases but may affect children and their families inducing depression, anxiety, burnout symptoms, and post-traumatic stress symptoms, as well as post-traumatic growth (PTG). The aim of this study was to investigate the co-occurrence of different aspects of such responses in parents of children that had undergone HSCT. MethodsQuestionnaires were completed by 260 parents (146 mothers and 114 fathers) 11-198 months after HSCT: the Hospital Anxiety and Depression Scale, the Shirom-Melamed Burnout Questionnaire, the post-traumatic stress disorders checklist, civilian version, and the PTG inventory. Additional variables were also investigated: perceived support, time elapsed since HSCT, job stress, partner-relationship satisfaction, trauma appraisal, and the child's health problems. A hierarchical cluster analysis and a k-means cluster analysis were used to identify patterns of psychological responses. ResultsFour clusters of parents with different psychological responses were identified. One cluster (n=40) significantly differed from the other groups and reported levels of depression, anxiety, burnout symptoms, and post-traumatic stress symptoms above the cut-off. In contrast, another cluster (n=66) reported higher levels of PTG than the other groups did. ConclusionsThis study shows a subgroup of parents maintaining high levels of several aspects of distress years after HSCT. Differences between clusters might be explained by differences in perceived support, the child's health problems, job stress, and partner-relationship satisfaction.
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| 12. |
- Aleksandrova, Krasimira, et al.
(författare)
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Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer
- 2014
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Ingår i: Hepatology. - : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 60:3, s. 858-871
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Tidskriftsartikel (refereegranskat)abstract
- Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.
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| 13. |
- Borné, Yan, et al.
(författare)
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Cadmium Exposure and Incidence of Diabetes Mellitus - Results from the Malmo Diet and Cancer Study
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cadmium is a pollutant with multiple adverse health effects: renal dysfunction, osteoporosis and fractures, cancer, and probably cardiovascular disease. Some studies have reported associations between cadmium and impaired fasting glucose and diabetes. However, this relationship is controversial and there is a lack of longitudinal studies. Objectives: To examine prospectively whether cadmium in blood is associated with incidence of diabetes mellitus. Methods: The study population consists of 4585 subjects without history of diabetes (aged 46 to 67 years, 60% women), who participated in the Malmo Diet and Cancer study during 1991-1994. Blood cadmium levels were estimated from hematocrit and cadmium concentrations in erythrocytes. Incident cases of diabetes were identified from national and local diabetes registers. Results: Cadmium concentrations in blood were not associated with blood glucose and insulin levels at the baseline examination. However, cadmium was positively associated with HbA1c in former smokers and current smokers. During a mean follow-up of 15.2 +/- 4.2 years, 622 (299 men and 323 women) were diagnosed with new-onset of diabetes. The incidence of diabetes was not significantly associated with blood cadmium level at baseline, neither in men or women. The hazard ratio (4th vs 1st quartile) was 1.11 (95% confidence interval 0.82-1.49), when adjusted for potential confounders. Conclusions: Elevated blood cadmium levels are not associated with increased incidence of diabetes. The positive association between HbA1c and blood cadmium levels has a likely explanation in mechanisms related to erythrocyte turnover and smoking.
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| 14. |
- Skalkidou, Alkistis, 1977-, et al.
(författare)
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O-058 46thCongress of the International Society of Paediatric Oncology (SIOP) 2014
- 2014
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 61:S2, s. S121-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives:Birth weight has been explored as a risk factor for several types of childhood (0-14 years) cancer. This nationwide Swedish cohort study aims to evaluate the associationbetween crude and adjusted characteristics of fetal growth (birth weight, length, headcircumference, ponderal index, small-SGA, appropriate-AGA and large for gestational age-LGA) and non-Hodgkin lymphoma (NHL) risk.Methods:All 3,444,136 singleton live births were included, among whom 515 incident NHLcases aged 0-14 years were diagnosed in 1973-2007, as identified through linkage with theSwedish Cancer Register. Proportional hazards models were used to estimate the HazardRatio (HR) and 95% confidence intervals (95% CI) of NHL. The core multivariable modelincluded infant sex, maternal education and maternal age at delivery, birth order of the indexchild (1þchild) and gestational age, the latter omitted in the analyses with SGA, AGA, LGAvariables, as appropriate.Results:Male sex was associated with a doubled NHL risk (HR¼2.00, 95% CI: 1.66-2.41).LGA birth weight, but not birth weightper se, was associated with an 80% increase in NHLrisk (HR¼1.83, 95%CI: 1.20-2.79). In the subgroup analyses by sex, the latter associationwas confined particularly to females (HR¼3.37, 95% CI: 1.90-5.97). Other growth variableswere not consistently associated with NHL risk, prossibly due to smaller variation ormeasurement errors.Conclusions:Fetal macrosomy seems to represent a considerable risk factor for childhoodNHL, whereas its effect may differ by gender. An approach to assess the association solelyusing crude birth weight, as a proxy, seems inadequate, given that more elaborate LGA indicesmay portray accelerated intrauterine growth as a more meaningful component. Future studiesshould aim at disentangling the physiological mechanisms underlying the relevance of sex-specific associations.
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| 15. |
- Femel, Julia, 1986-
(författare)
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Therapeutic Cancer Vaccines Targeting Molecules Associated with Tumor Angiogenesis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Induction of an endogenous antibody response by therapeutic vaccination could provide an alternative to cost-intensive monoclonal antibody-based treatments for cancer. Since the target of a cancer vaccine will most likely be a self-antigen, self-tolerance of the immune system must be circumvented. Using fusion proteins consisting of the self-antigen to be targeted and a part derived from a foreign antigen, it is possible to break tolerance against the self-antigen. Furthermore, a potent adjuvant is required to support an immune response against a self-molecule. Currently no adjuvant suitable for this purpose is approved for use in humans.This thesis describes the development of a therapeutic vaccine targeting the vasculature of tumors. As tumor cells have developed strategies to escape immune surveillance, targeting of molecules associated with the tumor stroma is an interesting alternative. The alternatively spliced extra domain-A and B (ED-A and ED-B) of fibronectin and the glycan-binding protein galectin-1 are selectively expressed during events of tumor angiogenesis. We have designed recombinant proteins to target ED-B, ED-A and galectin-1, containing bacterial thioredoxin (TRX) as a non-self part, resulting in TRX-EDB, TRX-EDA and TRX-Gal-1. Vaccination against ED-B induced anti-ED-B antibodies and inhibited growth of subcutaneous fibrosarcoma. Immunization against ED-A decreased tumor burden and reduced the number of lung metastases in the MMTV-PyMT model for metastatic mammary carcinoma in a therapeutic setting. Analysis of the tumor tissue from ED-B and ED-A-immunized mice indicated an attack of the tumor vasculature by the immune system. Finally, we show that galectin-1 immunization reduced tumor burden and increased leukocyte numbers in the tumor tissue. Galectin-1 is pro-angiogenic and immunosuppressive, and therefore allows simultaneous targeting of fundamental characteristics of tumorigenesis. We furthermore show that the biodegradable squalene-based Montanide ISA 720 combined with CpG oligo 1826 (M720/CpG) is at least as potent as Freund’s adjuvant with respect to breaking self-tolerance, when comparing several immunological parameters. Freund’s is a potent but toxic adjuvant used in the majority of preclinical studies.The work presented in this thesis shows that therapeutic cancer vaccines targeting the tumor vasculature are a feasible and promising approach for cancer therapy.
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| 16. |
- Johansson, Ann-Caroline, et al.
(författare)
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Illness perceptions in relation to experiences of contemporary cancer care settings among colorectal cancer survivors and their partners
- 2014
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Ingår i: International Journal of Qualitative Studies on Health and Well-Being. - : Informa UK Limited. - 1748-2623 .- 1748-2631. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Illness is constituted by subjective experiences of symptoms and their psychosocial consequences. Illness perceptions concern people's lay beliefs about understandings and interpretation of a disease and expectations as to disease outcome. Our knowledge about illness perceptions and coping in relation to the cancer care context among persons with colorectal cancer (CRC) and their partners is incomplete. The aim of the present study was to explore illness perceptions in relation to contemporary cancer care settings among CRC survivors and partners. The present research focused on illness rather than disease, implying that personal experiences are central to the methodology. The grounded theory method used is that presented by Kathy Charmaz. The present results explore illness perceptions in the early recovery phase after being diagnosed and treated for cancer in a contemporary cancer care setting. The core category outlook on the cancer diagnosis when quickly informed, treated, and discharged illustrates the illness perceptions of survivors and partners as well as the environment in which they were found. The cancer care environment is presented in the conceptual category experiencing contemporary cancer care settings. Receiving treatment quickly and without waiting was a positive experience for both partners and survivors; however partners experienced the information as massive and as causing concern. The period after discharge was being marked by uncertainty and loneliness, and partners tended to experience non-continuity in care as more problematic than the survivor did. The results showed different illness perceptions and a mismatch between illness perceptions among survivors and partners, presented in the conceptual category outlook on the cancer diagnosis. One illness perception, here presented among partners, focused on seeing the cancer diagnosis as a permanent life-changing event. The other illness perception, here presented among survivors, concentrated on leaving the cancer diagnosis behind and moving forward. The importance of illness perceptions among survivors, and the differences in illness perceptions between survivors and partners, should be recognized by healthcare professionals to achieve the goals of person-centered contemporary cancer care.
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| 17. |
- Markt, Sarah C., et al.
(författare)
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Genetic Variation Across C-Reactive Protein and Risk of Prostate Cancer
- 2014
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Ingår i: The Prostate. - : Wiley-Blackwell. - 0270-4137 .- 1097-0045. ; 74:10, s. 1034-1042
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. Inflammation has been hypothesized to play an important etiological role in the initiation or progression of prostate cancer. Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk of prostate cancer. We investigated the role of genetic variation in CRP and prostate cancer, under the hypothesis that variants may alter risk of disease.METHODS. We undertook a case-control study nested within the prospective Physicians' Health Study among 1,286 men with incident prostate cancer and 1,264 controls. Four single-nucleotide polymorphisms (SNPs) were selected to capture the common genetic variation across CRP (r(2) > 0.8). We used unconditional logistic regression to assess the association between each SNP and risk of prostate cancer. Linear regression models explored associations between each genotype and plasma CRP levels.RESULTS. None of the CRP SNPs were associated with prostate cancer overall. Individuals with one copy of the minor allele (C) in rs1800947 had an increased risk of high-grade prostate cancer (OR: 1.7; 95% CI: 1.1-2.8), and significantly lower mean CRP levels (P-value < 0.001), however, we found no significant association with lethal disease. Mean CRP levels were significantly elevated in men with one or two copies of the minor allele in rs3093075 and rs1417939, but these were unrelated to prostate cancer risk.CONCLUSION. Our findings suggest that SNPs in the CRP gene are not associated with risk of overall or lethal prostate cancer. Polymorphisms in CRP rs1800947 may be associated with higher grade disease, but our results require replication in other cohorts.
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| 18. |
- Moll, Guido, et al.
(författare)
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Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties?
- 2014
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 32:9, s. 2430-2442
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Tidskriftsartikel (refereegranskat)abstract
- We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties. Freeze-thawed MSCs demonstrated reduced responsiveness to proinflammatory stimuli, an impaired production of anti-inflammatory mediators, increased triggering of the IBMIR, and a strong activation of the complement cascade compared to fresh cells. This resulted in twice the efficiency in lysis of thawed MSCs after 1 hour of serum exposure. We found a 50% and 80% reduction in viable cells with freshly detached as opposed to thawed in vitro cells, indicating a small benefit for fresh cells. In evaluation of clinical response, we report a trend that fresh cells, and cells of low passage, demonstrate improved clinical outcome. Patients treated with freshly harvested cells in low passage had a 100% response rate, twice the response rate of 50% observed in a comparable group of patients treated with freeze-thawed cells at higher passage. We conclude that cryobanked MSCs have reduced immunomodulatory and blood regulatory properties directly after thawing, resulting in faster complement-mediated elimination after blood exposure. These changes seem to be paired by differences in therapeutic efficacy in treatment of immune ailments after hematopoietic stem cell transplantation.
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| 19. |
- Näppä, Ulla, 1960-
(författare)
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Dilemmas in palliative chemotherapy when approaching end-of-life
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background When cure is no longer possible, medical care should aim for a transition to palliative care regardless of disease. Patients with incurable cancer are often treated with palliative chemotherapy (PCT), starting with the intent to prolong life and increase quality of life. Eventually, in the late stages of the disease, the patient reaches a transition phase when further PCT neither prolongs life nor adds any predominantly positive effects.Aim of the thesisStudy I: To analyse the proportion of patients with incurable cancer who received palliative chemotherapy during the last month of life, and to identify their discriminative characteristics.Study II: To develop a questionnaire assessing performance status in palliative chemotherapy, and to test its psychometric properties.Study III: To explore challenging situations experienced by registered nurses when administering palliative chemotherapy to patients with incurable cancer.Study IV: To investigate whether routine use of the Performance Status in Palliative Chemotherapy (PSPC) questionnaire in PCT would affect the proportion of patients receiving PCT during the last month of life, hospital admissions, notifications of performance status, documented decisions of ceasing PCT in the medical records, and/or place of death. A secondary aim was to gather registered nurses’ experiences of PSPC in clinical use.Methods In Studies I and IV, information from the medical records of deceased patients with epithelial cancers was used in descriptive analyses of the proportions of patients receiving PCT in counties in northernmost Sweden. A quantitative design was chosen, using non-parametric statistical methods. In Study II, a brief patient-completed questionnaire assessing performance status was developed and psychometrically tested. In Study III, data from research interviews with registered nurses were analysed qualitatively with a narrative thematic approach.Results Studies I and IV showed that about 25% of patients receiving PCT were treated during the last month of life. This group of patients had more hospital admissions, were less likely to die at home, and had fewer instances of documentation of the decision to cease PCT. The questionnaire developed in Study II was shown to have acceptable psychometric qualities such as reliability, validity, and sensitivity to detect deterioration in performance status. Study IV showed that the questionnaire gave nurses valuable information about patients’ performance status. The results also showed that 97% of nurses and 48% of physicians documented their patients’ performance status in the medical records. Study III demonstrated that when nurses administered PCT they considered futile, they could experience dilemmas created by the unforeseeable outcomes of PCT or stemming from insufficient communication between nurses, patients, next-of-kin, and physicians.Conclusions Administration of PCT can create dilemmatic situations for both the patient and medical staff when approaching end-of-life. This is underlined by the finding that some 25% of treated patients received their last round of PCT as late as during the last month of life. The decisions to cease PCT were less likely to be documented for patients who had received PCT within a month before death. Nurses described situations where they felt they were in the middle of the decision-making process regarding whether or not to continue PCT. They found the treatments were given on the authority of someone else; the physician’s recommendation or the patient’s and/or relatives’ request.The unpredictability of PCT was a continuous theme in the work described in this thesis, emphasizing the necessity of individually assessing every patient before PCT in order to minimize the risk of futile treatments. The attempt to develop a reliable and valid questionnaire for systematic assessment of performance status has increased future possibilities to monitor this parameter in PCT when approaching end-of-life. The questionnaire developed as part of this thesis has provided nurses with increased knowledge of patients’ performance status. If routinely used, it may help decrease the proportion of patients receiving PCT during the last month of life, though this remains to be rigorously proven. Further research efforts are needed to progress in the task of optimizing rather than maximizing the use of PCT when approaching end-of-life.
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| 20. |
- Ottosson, Sandra, 1981-, et al.
(författare)
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Weight and body mass index in relation to irradiated volume and to overall survival in patients with oropharyngeal cancer: a retrospective cohort study
- 2014
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Ingår i: Radiation Oncology. - 1748-717X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight loss is a common problem in patients with Squamous Cell Carcinoma of the Head and Neck (SCCHN) treated with radiotherapy (RT). The aims of the present study were to determine if treated volume (TV), as a measure of the radiation dose burden, can predict weight loss in patients with oropharyngeal cancer and to analyze weight loss and body mass index (BMI) in the same patient group in relation to 5-year overall survival. Methods: The ARTSCAN trial is a prospective, randomized, multicenter trial in patients with SCCHN. Nutritional data from the ARTSCAN trial were analyzed retrospectively using univariate and multivariate statistical methods based on information on percentage weight loss from the start of RT up to five months after the termination of RT (study cohort 1, n = 232) and information on patients' BMI at the start of RT (study cohort 2, n = 203). TV was defined as the volume of the patient receiving at least 95% of the prescribed dose. TV64.6 (Gy) encompasses macroscopic tumor and TV43.7 (Gy) elective lymph nodes of the neck. Results: TV64.6 Gy and TV43.7 Gy were both significantly correlated with higher weight loss up to five months after the termination of RT in study cohort 1 (p < 0.001 for both). BMI at the start of RT was shown to be a prognostic factor for 5-year overall survival in study cohort 2 but weight loss was not. The hazard ratios and 95% confidence intervals were 3.78 (1.46-9.75) and 2.57 (1.43-4.62) in patients with underweight and normal weight, respectively. Conclusions: TV can predict weight loss during RT in patients with oropharyngeal cancer regardless of clinical stage. A high BMI (>25 kg/m(2)) at the start of RT is positively associated with survival in patients with oropharyngeal cancer.
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