| 1. |
- Fjällskog, Marie-Louise, et al.
(författare)
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Upregulated expression of PDGF receptor beta in endocrine pancreatic tumors and metastases compared to normal endocrine pancreas
- 2007
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 46:6, s. 741-746
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor receptor (PDGFR) beta signaling is involved in autocrine growth stimulation of tumor cells, tumor angiogenesis and regulation of tumor interstitial fluid pressure. Development of PDGFR antagonists has further increased the interest for PDGFR as targets for anticancer treatments. Malignant endocrine pancreatic tumors (EPTs) express PDGFR beta both in stroma and on tumor cells. To investigate the role of PDGFR beta signaling in EPTs we compared PDGFR beta expression in normal endocrine pancreas to malignant EPTs and metastases. PDGFR beta expression was examined by immunohistochemistry using specific polyclonal antibodies in ten tissue samples from normal endocrine pancreas, 21 from primary EPTs and 19 from metastases. In eight patients we compared the expression in normal endocrine pancreas to the corresponding primary tumor and metastases, in two patients normal tissue to the primary tumor and in 11 patients primary tumors to the corresponding metastases. Six of ten tissues containing normal pancreas stained negative for PDGFR beta on endocrine cells, while seven of ten stained positive in the stroma. Eighteen of 21 (86%) primary tumors stained positive for PDGFR beta on tumor cells and all had positive stroma stainings. All 19 metastases stained positive for PDGFR beta on tumor cells and in evaluable stroma (n=16). We have found that PDGFR beta is more frequently expressed in primary EPTs and metastases as compared to normal endocrine pancreatic tissue. This is also true for PDGFR beta expression in the corresponding stroma. We suggest that new therapeutic options to inhibit the growth and spread of EPTs could include targeting of PDGFR beta.
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| 2. |
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| 3. |
- Hessman, Ola, et al.
(författare)
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High success rate of parathyroid reoperation may be achieved with improved localization diagnosis
- 2008
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:5, s. 774-81; discussion 782
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery, preoperative imaging studies have been increasingly adopted. We report the use of consistently applied localization diagnosis to yield high success rates in parathyroid reoperations. METHODS: Parathyroid reoperation was performed after previous parathyroid surgery in 144 patients with nonmalignant hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients who underwent parathyroid reoperation and 14 patients who were subjected to thyroid surgery before primary parathyroid operation were investigated with sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was considered adequate, additional studies were generally not obtained. RESULTS: Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all patients with previous parathyroid surgery. In patients operated from year 2000, MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and 87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q-PTH analyses provided accurate localization or regionalization in 11 of 11 recently selected patients. Q-PTH analyses in fine-needle aspirations verified parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide when operations could be terminated. In patients subjected to the algorithm of imaging procedures, reversal of hypercalcemia and apparent cure was obtained after the reoperation in 45 of 46 patients with previous parathyroid surgery, implying a success rate of 98%, and in all patients with previous thyroid surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can be improved by consistently applied sensitive methods of preoperative imaging, and reoperative procedures may then achieve nearly the same success rates as primary operations.
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| 4. |
- Lindberg, Daniel, et al.
(författare)
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Cyclin-dependent kinase 4 (CDK4) expression in pancreatic endocrine tumors
- 2007
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 86:2, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Pancreatic endocrine tumors (PETs) occur sporadically, in association with the multiple endocrine neoplasia type 1 (MEN1) and the von Hippel-Lindau syndromes. CDK4 is central to the cell cycle control in pancreatic cells, and we have assessed whether CDK4 expression is deregulated in 18 human sporadic or familial PETs. Methods: Real-time quantitative PCR, immunohistochemistry, DNA sequencing, and Western blot analysis were used. Results: CDK4 mRNA was expressed in all PETs within the range of the arbitrary control. CDK4 protein was absent in normal pancreatic islets but distinctly expressed in all PETs as determined by immunohistochemistry. CDK4 expression was confirmed by Western blot analysis. No significant differences of CDK4 expression were observed between the groups of benign and malignant PETs or between tumors with or without MEN1 gene mutations. CDK4 expression was not due to gene amplification, and no mutations were identified in coding exons and RNA splice sites. c-Myc is known to be overexpressed in PETs and directly augments CDK4 expression in other cell types. Analysis of consecutive tissue sections for CDK4 and c-Myc showed overlapping homo- or heterogeneous immunostaining in all 18 PETs. Conclusion: We conclude that CDK4 and c-Myc is generally expressed in benign and malignant PETs, and regardless of MEN1 mutation-al status. Targeting of CDK4 may present an alternative to traditional chemotherapy of PETs in the future.
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| 5. |
- Segersten, Ulrika, et al.
(författare)
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25-hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-hydroxylated vitamin D analogue
- 2005
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 7, s. R980-R986
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated.METHODS:The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells.RESULTS:1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3.CONCLUSION:These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed.
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| 6. |
- Stålberg, Peter, et al.
(författare)
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Surgical treatment of Graves' disease : evidence-based approach.
- 2008
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 32:7, s. 1269-77
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment of Graves disease (GD) is still controversial. Surgery is one treatment option along with radioactive iodine (RAI) and antithyroid medication. In this evidence-based review, we examine four issues: (1) Is surgery better than RAI or long-term antithyroid medication? (2) What is the recommended surgical approach? (3) How does the presence of Graves' ophthalmopathy (GO) influence the role of surgery? (4) What is the role of surgery in children with GD? METHODS: We conducted a systematic review of the literature using evidence-based criteria regarding these four issues. RESULTS: (1) There are no recommendations reaching any grade of evidence for which treatment to choose for adults with GD. (2) Total thyroidectomy has complication rates equal to those seen with lesser resections but it has higher cure rates and negligible recurrence rates (Level I-IV data leading to a grade A recommendation). (3) Data support surgery when severe GO is present, but RAI combined with glucocorticoids may be equally safe (Level II-IV data, grade B recommendation). The extent of thyroid resection does not influence the outcome of GO (Level II data, grade B recommendation). (4) Based on the available data, definitive treatment can be advocated for children (Level IV data, grade C recommendation) using either RAI or surgery. No recommendation can be given as to whether RAI or surgery is preferred owing to the lack of studies addressing this issue. Increased cancer risk with RAI in children below the age of 5 years supports surgery in this setting (Level I data, grade A recommendation). CONCLUSION: If surgery is considered for definitive management, evidence-based criteria support total thyroidectomy as the surgical technique of choice for GD. Available evidence also supports surgery in the presence of severe endocrine GO. Children with GD should be treated with an ablative strategy. Whether this is achieved by total thyroidectomy or RAI may still be debatable. Data on long-term cancer risk are missing or conflicting; and until RAI has proven harmless in children, we continue to recommend surgery in this group.
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| 7. |
- Åkerström, Göran, et al.
(författare)
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Gastrointestinal carcinoids
- 2009
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Ingår i: Endocrine surgery. - London : Saunders. - 9780702030161 ; , s. 163-169
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Bokkapitel (populärvet., debatt m.m.)
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| 8. |
- Åkerström, Göran, et al.
(författare)
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Gastrointestinal carcinoids
- 2005
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Ingår i: Endocrine Surgery. - : Elsevier Ltd Edinburgh. ; , s. 163-197
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Åkerström, Göran, et al.
(författare)
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Management of midgut carcinoids
- 2005
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Ingår i: J Surg Oncol. ; 89:3, s. 161-169
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 10. |
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