| 1. |
- Hallgren, Oskar, et al.
(författare)
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Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients
- 2012
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. Results: The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Conclusions: Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD.
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| 2. |
- Löfdahl, Elisabet, et al.
(författare)
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Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region.
- 2012
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Ingår i: Radiation oncology (London, England). - 1748-717X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. METHODS: Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. RESULTS: The median accumulated dose was 1.9 Gy (1.5--2.2 Gy) to the hypothalamus and 2.4 Gy (1.8--3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0--9.3 Gy and 33.5--46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. CONCLUSION: In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls.
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| 3. |
- Löfdahl, Hedvig Elisabet
(författare)
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Risk factors and prevention of esophageal cancer
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Esophageal cancer is the eighth most common cancer in the world, consisting of two major histological types: squamous cell carcinoma (dominant globally) and adenocarcinoma (rapidly increasing in incidence in the Western world during the last decades). Established risk factors for adenocarcinoma are gastroesophageal reflux symptoms, obesity and tobacco smoking, whereas squamous cell carcinoma is mainly associated with tobacco smoking and excessive alcohol intake. Esophageal cancer predominantly affects men; the gender difference in squamous cell carcinoma cases is entirely explained by the higher prevalence of risk factors in men, but the striking 7:1 sex ratio in adenocarcinoma remains unexplained. Esophageal cancer carries a very poor prognosis and despite efforts to improve survival the overall 5-year survival rate is still less than 10%, emphasizing the need for preventive factors. This thesis focuses on the etiology of esophageal cancer and the unexplained male predominance in esophageal adenocarcinoma. The first paper investigates differences in risk factor profiles between women and men as a possible explanation for the male predominance in esophageal and cardiac adenocarcinoma. The paper was based on a nationwide population-based case-control study of all newly diagnosed cases of adenocarcinoma (n=451) and corresponding controls (n=816) in Sweden between 1994-1997. Contradictory to the hypothesis, the point odds ratios (OR) did not indicate any weaker association of the established risk factors reflux, obesity and tobacco smoking with risk of esophageal adenocarcinoma in women (4.6, 10.3, and 5.3, respectively) compared to men (3.4, 5.4, and 2.8, respectively). Protective factors such as a high intake of fruit and vegetables or infection with Helicobacter pylori showed no stronger protective effect in women. Thus, gender differences in the exposure to known risk factors do not seem to explain the male predominance in esophageal or cardia adenocarcinoma. The second paper investigated if the higher incidence rate of esophageal adenocarcinoma in the United Kingdom compared to Sweden is explained by a higher population prevalence of established risk factors. Investigations were based on identical questionnaires filled out by a random sample of the English (n=3633) and Swedish (n=1483) populations. The prevalence of gastroesophageal reflux symptoms and obesity were significantly higher in the English population (OR 2.0, 95% CI 1.6-2.4 and OR 1.8, 95% CI 1.5-2.1), suggesting that the higher incidence of esophageal adenocarcinoma in the United Kingdom is at least partly due to the higher population prevalence of well-established risk factors. The third paper investigates why surgical intervention of reflux does not provide protection against esophageal adenocarcinoma. All esophageal or cardia adenocarcinoma cases among antireflux operated patients in Sweden in 1965-2006 were identified and compared with matched controls from the same antireflux cohort. Recurrence of reflux after surgery was a risk factor for esophageal adenocarcinoma (OR 3.1, 95% CI 1.5-6.3), while BMI, tobacco smoking and type of antireflux surgery appeared to be of lesser importance. Recurrent reflux can explain the lack of a cancer protective effect of antireflux surgery and endoscopic surveillance might be an option for these patients. The fourth paper investigates the association between infection with human papillomavirus (HPV) and tumor location in the esophagus. The hypothesis is based on an oral route of transmission and an association between HPV and oropharyngeal squamous cell carcinoma. Available tumor material from esophageal squamous cell carcinomas in the Stockholm County in 1999-2006 was collected and examined for presence of HPV using multiplex polymerase chain reaction (PCR) with Luminex. No increased occurrence of HPV DNA was observed in esophageal squamous cell carcinomas located in the proximal compared to a more distal part of the esophagus. The prevalence of HPV DNA (10%) was low, and the identified HPV did not seem to be biologically active, based on p16INK4a data.
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| 4. |
- Olsson, Erik, 1960, et al.
(författare)
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Hippocampal volumes in patients exposed to low-dose radiation to the basal brain. A case--control study in long-term survivors from cancer in the head and neck region.
- 2012
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Ingår i: Radiation oncology (London, England). - 1748-717X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: An earlier study from our group of long time survivors of head and neck cancer who had received a low radiation dose to the hypothalamic-pituitary region, with no signs of recurrence or pituitary dysfunction, had their quality of life (QoL) compromised as compared with matched healthy controls. Hippocampal changes have been shown to accompany several psychiatric conditions and the aim of the present study was to test whether the patients' lowered QoL was coupled to a reduction in hippocampal volume. METHODS: Patients (11 men and 4 women, age 31--65) treated for head and neck cancer 4--10 years earlier and with no sign of recurrence or pituitary dysfunction, and 15 matched controls were included. The estimated radiation doses to the basal brain including the hippocampus (1.5 -- 9.3 Gy) had been calculated in the earlier study. The hippocampal volumetry was done on coronal sections from a 1.5 T MRI scanner. Measurements were done by two independent raters, blinded to patients and controls, using a custom method for computer assisted manual segmentation. The volumes were normalized for intracranial volume which was also measured manually. The paired t test and Wilcoxon's signed rank test were used for the main statistical analysis. RESULTS: There was no significant difference with respect to left, right or total hippocampal volume between patients and controls. All mean differences were close to zero, and the two-tailed 95% confidence interval for the difference in total, normalized volume does not include a larger than 8% deficit in the patients. CONCLUSION: The study gives solid evidence against the hypothesis that the patients' lowered quality of life was due to a major reduction of hippocampal volume.
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