| 1. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
- 2007
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Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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| 2. |
- Adolfsson, Jan, et al.
(författare)
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Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
- 2007
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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| 3. |
- Bondjers, Cecilia, 1974, et al.
(författare)
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Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes.
- 2006
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Ingår i: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. - : Wiley. - 1530-6860. ; 20:10, s. 1703-5
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Tidskriftsartikel (refereegranskat)abstract
- Normal blood microvessels are lined by pericytes, which contribute to microvessel development and stability through mechanisms that are poorly understood. Pericyte deficiency has been implicated in the pathogenesis of microvascular abnormalities associated with diabetes and tumors. However, the unambiguous identification of pericytes is still a problem because of cellular heterogeneity and few available molecular markers. Here we describe an approach to identify pericyte markers based on transcription profiling of pericyte-deficient brain microvessels isolated from platelet-derived growth factor (PDGF-B)-/- and PDGF beta receptor (PDGFRbeta)-/- mouse mutants. The approach was validated by the identification of known pericyte markers among the most down-regulated genes in PDGF-B-/- and PDGFRbeta-/- microvessels. Of candidates for novel pericyte markers, we selected ATP-sensitive potassium-channel Kir6.1 (also known as Kcnj8) and sulfonylurea receptor 2, (SUR2, also known as Abcc9), both part of the same channel complex, as well as delta homologue 1 (DLK1) for in situ hybridization, which demonstrated their specific expression in brain pericytes of mouse embryos. We also show that Kir6.1 is highly expressed in pericytes in brain but undetectable in pericytes in skin and heart. The three new brain pericyte markers are signaling molecules implicated in ion transport and intercellular signaling, potentially opening new windows on pericyte function in brain microvessels.
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| 4. |
- Hadrevi, Jenny, et al.
(författare)
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Evaluation of trapezius using proteomic methods
- 2007
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Ingår i: Sixth International Scientific Conference on Prevention of Work-Related Musculoskeletal Disorders. ; , s. 274-
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Konferensbidrag (refereegranskat)
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| 5. |
- Hellström, Mats, et al.
(författare)
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis.
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 445:7129, s. 776-80
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Tidskriftsartikel (refereegranskat)abstract
- In sprouting angiogenesis, specialized endothelial tip cells lead the outgrowth of blood-vessel sprouts towards gradients of vascular endothelial growth factor (VEGF)-A. VEGF-A is also essential for the induction of endothelial tip cells, but it is not known how single tip cells are selected to lead each vessel sprout, and how tip-cell numbers are determined. Here we present evidence that delta-like 4 (Dll4)-Notch1 signalling regulates the formation of appropriate numbers of tip cells to control vessel sprouting and branching in the mouse retina. We show that inhibition of Notch signalling using gamma-secretase inhibitors, genetic inactivation of one allele of the endothelial Notch ligand Dll4, or endothelial-specific genetic deletion of Notch1, all promote increased numbers of tip cells. Conversely, activation of Notch by a soluble jagged1 peptide leads to fewer tip cells and vessel branches. Dll4 and reporters of Notch signalling are distributed in a mosaic pattern among endothelial cells of actively sprouting retinal vessels. At this location, Notch1-deleted endothelial cells preferentially assume tip-cell characteristics. Together, our results suggest that Dll4-Notch1 signalling between the endothelial cells within the angiogenic sprout serves to restrict tip-cell formation in response to VEGF, thereby establishing the adequate ratio between tip and stalk cells required for correct sprouting and branching patterns. This model offers an explanation for the dose-dependency and haploinsufficiency of the Dll4 gene, and indicates that modulators of Dll4 or Notch signalling, such as gamma-secretase inhibitors developed for Alzheimer's disease, might find usage as pharmacological regulators of angiogenesis.
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| 6. |
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| 7. |
- Löfström, Björn, et al.
(författare)
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Myeloid leukaemia in systemic lupus erythematosus--a nested case-control study based on Swedish registers
- 2009
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 48:10, s. 1222-1226
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the risk factors for leukaemic transformation and myeloid leukaemia in patients with SLE. METHODS: A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case-control study in SLE patients who developed acute or chronic myeloid leukaemia was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed and bone marrow specimens were re-evaluated. A Medline search of previously published cases of SLE and myeloid leukaemia was performed. RESULTS: After confirmation of SLE diagnosis according to the ACR criteria, eight patients with SLE and myeloid leukaemia and 18 SLE controls were included in the study. Preceding leucopenia was significantly associated with leukaemia development, whereas other SLE manifestations were not. Two cases had a preceding bone marrow confirming myelodysplastic syndrome (MDS). Only two cases were significantly treated with cyclophosphamide or AZA. A Medline search resulted in only 15 previously published cases of coincident SLE and myeloid leukaemia. Preceding MDS was reported in five of these, whereas only eight had been treated with cytotoxic drugs. CONCLUSION: Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature. Leucopenia was a risk factor for myeloid leukaemia development and an MDS was frequently seen. Therefore bone marrow investigation should be considered in SLE patients with long-standing leucopenia and anaemia.
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| 8. |
- Tammela, Tuomas, et al.
(författare)
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Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation.
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 454:7204, s. 656-60
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.
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| 9. |
- Vesely, Stepan, et al.
(författare)
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Transurethral microwave thermotherapy of the prostate - Evaluation with MRI and analysis of parameters relevant to outcome.
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 42:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate morphological changes in the hyperplastic prostate tissue following transurethral microwave thermotherapy and to investigate the dependence of the treatment outcome on structural and physiological features of the prostate. Material and methods. In this prospective study, 13 patients with chronic urinary retention due to benign prostatic hyperplasia (BPH) underwent Coretherm (ProstaLund, Lund, Sweden) microwave thermotherapy. Prior to the treatment and 1 week and 6 months after, the patients were examined with MRI using morphologic, contrast medium-enhanced perfusion and diffusion-weighted imaging. Such advanced MRI techniques permit an assessment of parameters that have a hypothetical influence on microwave thermotherapy (e.g. prostate blood perfusion, water content and prostate microstructure). Results. Morphologic and perfusion MRI showed a clear prostatic tissue defect in all 13 patients after 1 week and in all 12 patients at 6 months' follow-up. The mean size of the defect was 22.5 cm3 (27%) (range 3.7-47.3 cm3) and 4.1 cm3 (1.1-10.1 cm3) at 1 week and 6 months, respectively. The cell kill volume was estimated to be 20.5±7.4 cm3 and correlated significantly with the size assessed by MRI at 1 week (r=0.8; p=0.002) and 6 months (r=0.69; p=0.05). At 6 months, the mean decrease in prostate volume was 20.1 cm3 (p<0.0001). The microstructure of the prostate expressed as the apparent diffusion coefficient was shown to have a strong influence on the treatment process. All patients (n=12) were catheter-free at 6 months. Another patient experienced persistent obstruction and underwent transurethral resection of the prostate. Conclusions. Coretherm microwave treatment leads to significant intraprostatic necrosis, which is detectable with MRI even 6 months after the treatment. Diffusion-weighted MRI is capable of identifying structural features of the prostate that can predict the length of treatment and the amount of energy needed.
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| 10. |
- Wallgard, Elisabet, et al.
(författare)
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Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature.
- 2008
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636 .- 1079-5642. ; 28:8, s. 1469-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Pathological angiogenesis is an integral component of many diseases. Antiangiogenesis and vascular targeting are therefore promising new therapeutic principles. However, few endothelial-specific putative drug targets have been identified, and information is still limited about endothelial-specific molecular processes. Here we aimed at determining the endothelial cell-specific core transcriptome in vivo. METHODS AND RESULTS: Analysis of publicly available microarray data identified a mixed vascular/lung cluster of 132 genes that correlated with known endothelial markers. Filtering against kidney glomerular/nonglomerular and brain vascular/nonvascular microarray profiles separated contaminating lung markers, leaving 58 genes with broad and specific microvascular expression. More than half of these have not previously been linked to endothelial functions or studied in detail before. The endothelial cell-specific expression of a selected subset of these, Eltd1, Gpr116, Ramp2, Slc9a3r2, Slc43a3, Rasip1, and NM_023516, was confirmed by real-time quantitative polymerase chain reaction and/or immunohistochemistry. CONCLUSIONS: We have used a combination of publicly available and own microarray data to identify 58 gene transcripts with broad yet specific expression in microvascular endothelium. Most of these have unknown functions, but many of them are predicted to be cell surface expressed or implicated in cell signaling processes and should therefore be explored as putative microvascular drug targets.
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