| 31. |
- Fougner, Stine L, et al.
(författare)
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The clinical response to somatostatin analogues in acromegaly correlates to the somatostatin receptor subtype 2a protein expression of the adenoma.
- 2008
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 68:3, s. 458-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G-protein alpha subunit (Gsalpha) mutation (gsp oncogene)-positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide.PATIENTS: Seventy-one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment.MEASUREMENTS: The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF-1 level after 6 months preoperative octreotide treatment was recorded.RESULTS: The acute octreotide response in non-pretreated patients and the preoperative long-term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response.CONCLUSION: The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down-regulation of SSTR2a during octreotide treatment.
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| 32. |
- Fougner, Stine Lyngvi, et al.
(författare)
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The expression of E-cadherin in somatotroph pituitary adenomas is related to tumor size, invasiveness, and somatostatin analog response
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:5, s. 2334-2342
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Appropriate cell-to-cell adhesion is fundamental for the epithelial phenotype of pituitary cells. Loss of the adhesion protein E-cadherin has been associated with invasiveness, metastasis, and poor prognosis in cancers of epithelial origin. In somatotroph adenomas, a variable and reduced expression of E-cadherin has been demonstrated. In addition, nuclear translocation of E-cadherin was found to correlate with pituitary tumor invasion.OBJECTIVE: The objective was to examine the protein expression of E-cadherin in somatotroph pituitary adenomas in relation to adenoma size, invasiveness, and somatostatin analog (SMS) efficacy.PATIENTS AND METHODS: Eighty-three patients were included, and 29 were treated preoperatively with SMS. Adenoma E-cadherin protein expression was analyzed by Western blot (61 patients) and immunohistochemistry (IHC) (80 patients) with antibodies directed against both extracellular and intracellular domains (IHC). The acute (direct surgery group) and long-term (preoperatively treated group) SMS responses were evaluated. Baseline tumor volume and invasiveness were measured on magnetic resonance imaging scans.RESULTS: Membranous E-cadherin was lost in several adenomas. Nine of these were nuclear E-cadherin positive. The E-cadherin protein expression correlated negatively to tumor size and positively to acute SMS response. Low E-cadherin levels (preoperatively treated group only) and loss of membranous E-cadherin correlated to tumor invasiveness. The E-cadherin level correlated positively to tumor reduction after SMS treatment, and adenomas with nuclear E-cadherin staining had lower IGF-I reduction and tumor shrinkage. Preoperatively treated adenomas had reduced E-cadherin protein levels, but the IHC expression was unaltered.CONCLUSION: Reduced E-cadherin expression may correlate to a dedifferentiated phenotype in the somatotroph pituitary adenomas.
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| 33. |
- Ghaderi Berntsson, Shala, 1964-, et al.
(författare)
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Case report : a novel deep intronic splice-altering variant in DMD as a cause of Becker muscular dystrophy
- 2023
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Ingår i: Frontiers in Genetics. - : Frontiers Media S.A.. - 1664-8021. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- We present the case of a male patient who was ultimately diagnosed with Becker muscular dystrophy (BMD; MIM# 300376) after the onset of muscle weakness in his teens progressively led to significant walking difficulties in his twenties. A genetic diagnosis was pursued but initial investigation revealed no aberrations in the dystrophin gene (DMD), although immunohistochemistry and Western blot analysis suggested the diagnosis of dystrophinopathy. Eventually, after more than 10 years, an RNA analysis captured abnormal splicing where 154 nucleotides from intron 43 were inserted between exon 43 and 44 resulting in a frameshift and a premature stop codon. Normal splicing of the DMD gene was also observed. Additionally, a novel variant c.6291–13537A>G in DMD was confirmed in the genomic DNA of the patient. The predicted function of the variant aligns with the mRNA results. To conclude, we here demonstrate that mRNA analysis can guide the diagnosis of non-coding genetic variants in DMD.
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| 34. |
- Guaraldi, Federica, et al.
(författare)
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Hypophysitis
- 2018. - 2
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Ingår i: Encyclopedia of Endocrine Diseases. - : Academic Press. - 9780128122006 ; , s. 325-338
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Bokkapitel (refereegranskat)
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| 35. |
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| 36. |
- Heck, Ansgar, et al.
(författare)
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Intensity of pituitary adenoma on T2-weighted magnetic resonance imaging predicts the response to octreotide treatment in newly diagnosed acromegaly
- 2012
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 77:1, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- Background Primary, preoperative medical treatment is an option in selected patients with acromegaly, but a subset of patients respond poorly. Valid prediction of response to somatostatin analogues (SA) might thus alter treatment stratification. The aims of this study were to assess whether T2 signal intensity could determine long-term response to first-line SA treatment and to assess clinical and biochemical baseline characteristics, as well as histological subtype in relation to the magnetic resonance imaging (MRI) appearances. Methods In 45 newly diagnosed patients, T2-weighted signal intensity of the tumour was classified into hypo-, iso- or hyperintense. Biochemical and clinical baseline variables for the three groups were compared. In 25 patients primarily treated with long-acting SA for a median of 6 months [interquartile range (IQR):155180 days], GH and IGF-1 reduction was assessed, and in 34 cases, immunohistochemical granulation pattern was evaluated. Results The results showed that 12 (27%) adenomas were hypointense, 15 (33%) isointense and 18 (40%) hyperintense. Median IGF-1 [ratio IGF-1/ULN; (upper limit of normal)] was 3.5 (2.34.9), 2.9 (2.63.8) and 1.9 (1.32.6), respectively (P = 0.006 for difference between groups). Median GH values (mu g/l) of a 3- to 5-point profile were 17.5 (6.135), 9.3 (6.032.5) and 4.1 (1.58.3), (P = 0.025). Median IGF-1 reduction (% of baseline) after first-line SA treatment was 51 (4970), 36 (1974) and 13 (542) (P = 0.03); median reduction in GH (% of baseline) was 86 (7294), 78 (6285) and 46 (170) (P = 0.02). T2 hyperintensity was associated with sparse granulation pattern on immunohistochemistry. Conclusion In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line SA treatment.
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| 37. |
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| 38. |
- Heck, Ansgar, et al.
(författare)
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Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly
- 2016
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 52:2, s. 333-343
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Tidskriftsartikel (refereegranskat)abstract
- In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = -0.67; p < 0.001) and IGF-1 (r = -0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = -0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern.
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| 39. |
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| 40. |
- Jotanovic, Jelena, et al.
(författare)
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Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors
- 2024
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Ingår i: Journal of the Endocrine Society. - : Oxford University Press. - 2472-1972. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- Although most pituitary neuroendocrine tumors (PitNETs)/pituitary adenomas remain intrasellar, a significant proportion of tumors show parasellar invasive growth and 6% to 8% infiltrate the bone structures, thus affecting the prognosis. There is an unmet need to identify novel markers that can predict the parasellar growth of PitNETs. Furthermore, mechanisms that regulate bone invasiveness of PitNETs and factors related to tumor vascularization are largely unknown.We used genome-wide mRNA analysis in a cohort of 77 patients with PitNETs of different types to explore the differences in gene expression patterns between invasive and noninvasive tumors with respect to the parasellar growth and regarding the rare phenomenon of bone invasiveness. Additionally, we studied the genes correlated to the contrast enhancement quotient, a novel radiological parameter of tumor vascularization.Most of the genes differentially expressed related to the parasellar growth were genes involved in tumor invasiveness. Differentially expressed genes associated with bone invasiveness are involved in NF-κB pathway and antitumoral immune response. Lack of clear clustering regarding the parasellar and bone invasiveness may be explained by the influence of the cell lineage-related genes in this heterogeneous cohort of PitNETs.Our transcriptomics analysis revealed differences in the molecular fingerprints between invasive, including bone invasive, and noninvasive PitNETs, although without clear clustering. The contrast enhancement quotient emerged as a radiological parameter of tumor vascularization, correlating with several angiogenesis-related genes. Several of the top genes related to the PitNET invasiveness and vascularization have potential prognostic and therapeutic application requiring further research.
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