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- Cunningham, Janet Lynn, 1974-
(författare)
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Tumour Biological Factors Characterizing Metastasizing Serotonin-producing Ileocaecal Carcinoids
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this study, metastasizing serotonin-producing ileocaecal carcinoid tumours (MSPCs) were examined for biological characteristics that could be used to define clinically relevant subgroups within this patient population. Possible targets for new treatment options were also explored.It was found that MSPCs share several biological characteristics such as expression of serotonin, tachykinins (TKs), chromogranin A, islet autoantigen-2 and connective tissue growth factor (CTGF). TKs and serotonin were demonstrated in the same endocrine tumours in the gut and lung. IA-2 expression was shown to be up-regulated in MSPCs, possibly in connection with active hormone secretion. CTGF expression was high in tumour areas adjacent to extensive stroma expressing alpha-smooth muscle actin. This indicated myofibroblast differentiation, which may be associated with fibrosis-related complications prevalent in patients with MSPCs. When compared with other endocrine tumours, MSPCs behaved as a relatively homogeneous group, though within the MSPC population several subgroups could be defined. Patients with tumours displaying either a solid growth pattern and/or a Ki67 index ≥1% had a less favourable prognosis than those who did not. Another group of patients, who had increased plasma TK concentrations, were more likely to suffer from severe diarrhea. This information should be considered when discussing clinical treatment and when undertaking tumour biological studies. New treatment possibilities, such as drugs that specifically target TK receptors and antibodies to CTGF, are also discussed.In conclusion, MSPCs comprise a clinically relevant tumour group with similar biological features that are distinct from other endocrine tumours. Subgroups of patients within this patient category can be defined which may be relevant when establishing prognosis and when selecting future treatment modalities.
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- Ekeblad, Sara, et al.
(författare)
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Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:10, s. 2986-2991
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
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- Fjällskog, Marie-Louise H., et al.
(författare)
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Treatment with Combined Streptozotocin and Liposomal Doxorubicin in Metastatic Endocrine Pancreatic Tumors
- 2008
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 88:1, s. 53-8
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with combined streptozotocin and liposomal doxorubicin is safe and efficient in patients with endocrine pancreatic tumors (EPTs). No cardiac toxicity was reported. BACKGROUND: The combination of streptozotocin and doxorubicin has been shown to be superior to streptozotocin and fluorouracil in the treatment of metastatic EPTs. However, the risk of cardiac toxicity from anthracyclins hampers the usefulness of the drug combination. Liposomal doxorubicin has a lower frequency of cardiac adverse events compared to doxorubicin. We wanted to assess the efficacy and safety of combined streptozotocin and liposomal doxorubicin in patients with metastatic EPTs. METHODS: Thirty patients with metastatic EPTs were recruited from three medical centers in Norway and Sweden during a time period of 3 years. All patients had histopathologically confirmed diagnoses and bidimensionally measurable lesions. 30 mg/m(2) of liposomal doxorubicin was administered on day 1 of each cycle. During the first course, 1 g of streptozotocin was given on 5 consecutive days. Thereafter, 2 g of streptozotocin was given on day 1 only. Treatment was repeated every 3 weeks. RESULTS: Twelve of 30 patients (40%) achieved an objective radiological response with a median duration of 9 months. Stabilization of disease was achieved in 17 of 30 patients (57%) for a median duration of 11 months. Only one patient had progressive disease as best response. The 2-year progression-free survival was 18% and the 2-year overall survival was 72%. The treatment was well tolerated. None of the patients experienced cardiac toxicity. CONCLUSION: We conclude that combined streptozotocin and liposomal doxorubicin is a safe and efficient treatment for EPTs. The efficacy seems to be comparable to that of combined streptozotocin and doxorubicin, whereas the cardiac toxicity clearly favors using the liposomal drug combination. 2008 S. Karger AG, Basel.
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- Franklin, Karl, et al.
(författare)
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Early life environment and snoring in adulthood
- 2008
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 9:1, s. 63-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life. METHODS: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%). RESULTS: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined. CONCLUSION: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood.
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- Gomez Real, F., et al.
(författare)
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Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey
- 2006
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Ingår i: Thorax.. ; 61:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m(2)). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m(2)); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m(2)) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.
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| 8. |
- Granberg, Dan, et al.
(författare)
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Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors
- 2007
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:2, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors. MATERIAL AND METHODS: Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome. RESULTS: Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations. CONCLUSION: Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.
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| 10. |
- Hellgren, Johan, 1965, et al.
(författare)
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Perennial non-infectious rhinitis--an independent risk factor for sleep disturbances in Asthma.
- 2007
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:5, s. 1015-20
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Tidskriftsartikel (refereegranskat)abstract
- Aim of the studyTo evaluate if perennial non-infectious rhinitis is associated with sleep disturbances in asthma.Materials and methodsThis is a questionnaire based study in a random population sample from Denmark, Estonia, Iceland, Norway and Sweden aged 30–54 yr. A total of 1127 individuals reporting asthma from an original random population sample of 16,191 were analysed regarding their quality of sleep in relation to perennial non-infectious rhinitis. Perennial non-infectious rhinitis was defined as having nasal symptoms such as nasal blockage and secretion in the absence of common cold, always. Asthma was defined as both ever having had asthma and having physician diagnosed asthma. Odds ratios (OR) for difficulties inducing sleep, difficulties maintaining sleep, early morning awakenings and daytime sleepiness were calculated in a multiple logistic regression controlling for other risk factors for sleep disturbances such as snoring, wheeze, obesity and smoking.ResultsThe response rate was 74%. A total of 189 (17%) of the subjects with asthma reported perennial non-infectious rhinitis. Perennial non-infectious rhinitis was associated with an increased OR for difficulties maintaining sleep (1.6 (95% confidence interval (CI) 1.1–2.3)), early morning awakenings (1.5 (95% CI 1.1–2.2)) and daytime sleepiness (1.8 (95% CI 1.2–2.9)). The result show that perennial non-infectious rhinitis is an independant risk factor for sleep disturbances in asthma.
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