| 1. |
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| 2. |
- Bümming, Per, 1965, et al.
(författare)
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Can the early reduction of tumour markers predict outcome in surgically treated sporadic medullary thyroid carcinoma?
- 2008
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Ingår i: Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie. - : Springer Science and Business Media LLC. - 1435-2443. ; 393:5, s. 699-703
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Patients with sporadic medullary thyroid carcinoma (MTC) have a variable clinical course. Our aim was to analyse the reduction of tumour markers after thyroidectomy with meticulous dissection and relate it to clinical outcome. MATERIALS AND METHODS: Twenty consecutive patients with palpable sporadic MTC underwent thyroidectomy with central and uni- or bilateral modified radical neck dissection; three were subjected to mediastinal dissection. Basal (b-) and stimulated (s-) calcitonin (CT) and carcinoembryonic antigen (CEA)-levels were measured before and 6-8 weeks after primary surgery, and the reduction of these tumour markers was determined. RESULTS: Median CT (b- and s-) were markedly reduced after surgery (98.5% and 99.1%, respectively), and CEA decreased 11 times. CT (b-) fell >99% in seven patients after surgery; in these and four additional patients, CT (s-) showed a similar reduction. During follow-up (median 52.5 months), two patients (stages IV B and C) died of MTC; they had <95% reduction of CT. Four patients (stage IV A) are alive with verified metastases. Eight patients (one stage III, seven stage IV A) are alive with hypercalcitoninemia. Five stages I-III patients and one stage IV A patient are disease-free. CONCLUSIONS: Thyroidectomy and meticulous dissection caused a pronounced reduction of tumour markers. A postoperative reduction of CT (s-) >/=97% seems to be associated with less aggressive clinical course, while CEA had lower predictive value.
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| 3. |
- Bümming, Per, 1965, et al.
(författare)
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Gastrointestinal stromal tumors regularly express synaptic vesicle proteins: evidence of a neuroendocrine phenotype.
- 2007
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Ingår i: Endocrine-related cancer. - 1351-0088. ; 14:3, s. 853-63
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal stromal tumors (GISTs) are thought to originate from the interstitial cells of Cajal, which share many properties with neurons of the gastrointestinal tract. Recently, we demonstrated expression of the hormone ghrelin in GIST. The aim of the present study was therefore to evaluate a possible neuroendocrine phenotype of GIST. Specimens from 41 GISTs were examined for the expression of 12 different synaptic vesicle proteins. Expression of synaptic-like microvesicle proteins, e.g., Synaptic vesicle protein 2 (SV2), synaptobrevin, synapsin 1, and amphiphysin was demonstrated in a majority of GISTs by immunohistochemistry, western blotting, and quantitative reversetranscriptase PCR. One-third of the tumors also expressed the large dense core vesicle protein vesicular monoamine transporter 1. Presence of microvesicles and dense core vesicles in GIST was confirmed by electron microscopy. The expression of synaptic-like microvesicle proteins in GIST was not related to risk profile or to KIT/platelet derived growth factor alpha (PDGFRA) mutational status. Thus, GISTs regularly express a subset of synaptic-like microvesicle proteins necessary for the regulated secretion of neurotransmitters and hormones. Expression of synaptic-like micro-vesicle proteins, ghrelin and peptide hormone receptors in GIST indicate a neuroendocrine phenotype and suggest novel possibilities to treat therapy-resistant GIST.
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| 4. |
- Bümming, Per, 1965, et al.
(författare)
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Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1
- 2006
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:5, s. 626-30
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Tidskriftsartikel (refereegranskat)abstract
- There is rapid evolution in the functional imaging of tumours. In two patients with concomitant pheochromocytoma and gastrointestinal stromal tumour (GIST), previously unrecognized tumours were visualized by combined 2-tracer positron emission tomography (PET), which also provided precise information about tumour type. PET imaging led to radical resection and the diagnoses were histopathologically confirmed. GISTs from the Carney patient and the patient with neurofibromatosis type 1 (NF1) both lacked KIT mutations.
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| 5. |
- Ekeblad, Sara, et al.
(författare)
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Gastrointestinal stromal tumors express the orexigen ghrelin
- 2006
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Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 13:3, s. 963-70
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Tidskriftsartikel (refereegranskat)abstract
- Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
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| 6. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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Long-term outcome of a large series of patients surgically treated for pheochromocytoma
- 2005
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Ingår i: Journal of internal medicine. - 0954-6820. ; 258:1, s. 55-66
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.
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| 7. |
- Lönnroth, Christina, 1946, et al.
(författare)
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Survival and erythropoietin receptor protein in tumours from patients randomly treated with rhEPO for palliative care.
- 2008
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Ingår i: Medical oncology (Northwood, London, England). - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 25:1, s. 22-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recombinant erythropoietin (rhEPOalpha) corrects anaemia, improves physical functioning and quality of life in cancer patients. However, published reports have suggested risks for tumour stimulation by provision EPO to patients with remaining tumour cells perhaps related to the presence of EPO receptor protein in tumour tissue. Therefore, the aim of the present study was to exclude a possibility that cancer patients who respond favourably to EPO treatment have mainly tumours with low EPO receptor protein expression. METHODS: Tumour tissue was evaluated in 87 patients out of 108 randomly allocated for treatment with rhEPOalpha (n = 50) versus controls (n = 58). Tumour cell proliferation (Ki-67 index) and EPO receptor protein expression were evaluated by immunohistochemistry. RESULTS: EPO treatment varied between 2 and 35 months, in doses between 10,000 and 40,000 Units/week. Ki-67 index did not differ between study and control patients before EPO treatment. Tumour tissue erythropoietin receptor protein was also similar between treated and untreated patients. Around 40% of tumour cells contained EPO receptors. Survival did not differ among EPO treated and control patients analysed as intention to treat, while survival was significantly improved in EPO treated patients per protocol treatment (P < 0.05). Ki-67 index and tumour tissue erythropoietin receptor protein did not predict survival, which systemic inflammation (ESR) did (P < 0.02). CONCLUSIONS: Our results support that reported risk to accelerate disease progression by EPO treatment in palliative care is not justified in patients with solid, gastrointestinal cancer despite tumour presence of EPO receptor protein.
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| 8. |
- Nilsson, Bengt E, 1949, et al.
(författare)
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Adjuvant imatinib treatment improves recurrence-free survival in patients with high-risk gastrointestinal stromal tumours (GIST)
- 2007
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:11, s. 1656-8
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Tidskriftsartikel (refereegranskat)abstract
- Palliative imatinib treatment has dramatically improved survival in patients with malignant gastrointestinal stromal tumours, particularly in patients with tumours harbouring activating KIT mutations. To evaluate the effectiveness of adjuvant imatinib after radical surgery, a consecutive series of patients with high-risk tumours (n=23) was compared with historic controls (n=48) who were treated with surgery alone. The mean follow-up period was over 3 years in both groups. Only 1 out of 23 patients (4%) in the adjuvant treatment group developed recurrent disease compared to 32 out of 48 patients (67%) in the control group. This preliminary study indicates that 1 year of adjuvant treatment with imatinib dramatically improves recurrence-free survival. Confirmation of these findings awaits the results of ongoing randomised studies.
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| 9. |
- Nilsson, Bengt E, 1949, et al.
(författare)
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Treatment of gastrointestinal stromal tumours: imatinib, sunitinib -- and then?
- 2009
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Ingår i: Expert opinion on investigational drugs. - : Informa Healthcare. - 1744-7658 .- 1354-3784. ; 18:4, s. 457-68
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Tidskriftsartikel (refereegranskat)abstract
- With the discovery of gain-of-function mutations of KIT in a majority of gastrointestinal stromal tumours (GIST) and access to the tailored tyrosine kinase inhibitor (TKI) imatinib, a new era in cancer therapy started. The drug caused marked tumour responses in most patients with advanced GISTs, but could also be used in an adjuvant setting after radical surgery or as downstaging treatment before intentionally curative surgery. With prolonged treatment imatinib resistance can develop, most likely due to secondary KIT mutations. In this situation the second-line TKI sunitinib is well suited to patients with KIT exon 9 mutations, or for patients without KIT/PDGFRA mutations (wild-type GIST). New treatment is required to treat imatinib or sunitinib resistance. New-generation TKIs have broader target profiles and increased activity against certain targets; but also new principles have been proposed, for example dose escalation, inhibition of downstream signalling molecules, HSP90 chaperon inhibition, transcriptional repression, combination with chemotherapy or receptor-mediated therapy of highly expressed cell surface receptors. Targeting of cancer stem cells may be another option.
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| 10. |
- Nyberg, Jenny, 1976, et al.
(författare)
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Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation.
- 2005
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Ingår i: The Journal of neuroscience : the official journal of the Society for Neuroscience. - : Society for Neuroscience. - 1529-2401. ; 25:7, s. 1816-25
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal dentate gyrus (DG) is an area of active proliferation and neurogenesis within the adult brain. The molecular events controlling adult cell genesis in the hippocampus essentially remain unknown. It has been reported previously that adult male and female rats from the strains Sprague Dawley (SD) and spontaneously hypertensive (SHR) have a marked difference in proliferation rates of cells in the hippocampal DG. To exploit this natural variability and identify potential regulators of cell genesis in the hippocampus, hippocampal gene expression from male SHR as well as male and female SD rats was analyzed using a cDNA array strategy. Hippocampal expression of the gene-encoding glucose-dependent insulinotropic polypeptide (GIP) varied strongly in parallel with cell-proliferation rates in the adult rat DG. Moreover, robust GIP immunoreactivity could be detected in the DG. The GIP receptor is expressed by cultured adult hippocampal progenitors and throughout the granule cell layer of the DG, including progenitor cells. Thus, these cells have the ability to respond to GIP. Indeed, exogenously delivered GIP induced proliferation of adult-derived hippocampal progenitors in vivo as well as in vitro, and adult GIP receptor knock-out mice exhibit a significantly lower number of newborn cells in the hippocampal DG compared with wild-type mice. This investigation demonstrates the presence of GIP in the brain for the first time and provides evidence for a regulatory function for GIP in progenitor cell proliferation.
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| 11. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Multiple lymph node metastases in a boy with primary testicular carcinoid, despite negative preoperative imaging procedures.
- 2005
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Ingår i: Journal of pediatric surgery. - : Elsevier BV. - 1531-5037 .- 0022-3468. ; 40:11
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Tidskriftsartikel (refereegranskat)abstract
- A testicular tumor in a 12-year-old boy proved to be a carcinoid tumor. An extensive investigation including a computed tomographic scan of the abdominal and pelvic region as well as both 123I-labeled metaiodobenzylguanidine and 111In-coupled octreotide scintigraphy was normal. Because histopathologic examination of the primary surgical specimen revealed tumor growth in the resection border of the spermatic vessels, a second operation with unilateral lymph node dissection was performed. Surprisingly, 3 lymph node metastases were found. No further treatment was given and the boy is alive without disease 9 years after surgery. This case illustrates that modern scintigraphic techniques do not always detect carcinoid tumors. Because carcinoids respond poorly to other treatment modalities, the importance of initial radical surgery including a meticulous examination of regional lymph nodes is emphasized.
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| 12. |
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| 13. |
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| 14. |
- Andersson, Ellinor, et al.
(författare)
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High-resolution genomic profiling reveals gain of chromosome 14 as a predictor of poor outcome in ileal carcinoids.
- 2009
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Ingår i: Endocrine-related cancer. - 1479-6821. ; 16:3, s. 953-66
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Tidskriftsartikel (refereegranskat)abstract
- Ileal carcinoids are malignant neuroendocrine tumours of the small intestine. The aim of this study was to obtain a high-resolution genomic profile of ileal carcinoids in order to define genetic changes important for tumour initiation, progression and survival. Forty-three patients with ileal carcinoids were investigated by high-resolution array-based comparative genomic hybridization. The average number of copy number alterations (CNAs) per tumour was 7.1 (range 1-22), with losses being more common than gains (ratio 1.4). The most frequent CNA was loss of chromosome 18 (74%). Other frequent CNAs were gain of chromosome 4, 5, 14 and 20, and loss of 11q22.1-q22.2, 11q22.3-q23.1 and 11q23.3, and loss of 16q12.2-q22.1 and 16q23.2-qter. Two distinct patterns of CNAs were found; the majority of tumours was characterized by loss of chromosome 18 while a subgroup of tumours had intact chromosome 18, but gain of chromosome 14. Survival analysis, using a series of Poisson regressions including recurrent CNAs, demonstrated that gain of chromosome 14 was a strong predictor of poor survival. In conclusion, high-resolution profiling demonstrated two separate patterns of CNAs in ileal carcinoids. The majority of tumours showed loss of chromosome 18, which most likely represents a primary event in the development and pathogenesis of tumours. A different genetic pathway is operative in a subgroup of tumours; this is characterized by gain of chromosome 14 and is strongly associated with poor prognosis. Predictive fluorescence in situ hybridization analysis of chromosome 14 status in patients with ileal carcinoids is suggested.
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| 15. |
- Andersson, Mattias K, 1979, et al.
(författare)
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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response
- 2008
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Ingår i: BMC Cell Biology. - : Springer Science and Business Media LLC. - 1471-2121. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias. The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing. In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types. RESULTS: FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues. The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types. Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types. Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells. The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation. Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells. CONCLUSION: Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies. The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions. Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer.
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| 16. |
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| 17. |
- Arvidsson, Yvonne, 1960, et al.
(författare)
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Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract.
- 2008
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Ingår i: Endocrine-related cancer. - 1351-0088. ; 15:2, s. 569-81
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed a correlation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence tumour cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.
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| 18. |
- Bernhardt, Peter, 1966, et al.
(författare)
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Effects of treatment with (177)Lu-DOTA-Tyr(3)-octreotate on uptake of subsequent injection in carcinoid-bearing nude mice.
- 2007
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Ingår i: Cancer biotherapy & radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:5, s. 644-53
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to analyze the effect therapeutic injections of (177)Lu-DOTA(0)-Tyr(3)]-octreotate (DOTATATE) had on the tumor uptake of a subsequent injection with (111)In-DOTATATE in GOT1-bearing nude mice. METHODS AND MATERIALS: Nude mice, xenografted with the human midgut carcinoid, GOT1, were first intravenously injected with a curative (30 MBq) or a suboptimal (7.5 MBq) amount of (177)Lu-DOTATATE. At various intervals thereafter (4-13 days), a second injection with (111)In-DOTATATE (0.5 MBq) was given. One (1) day after the second injection, the animals were sacrificed, tumor tissues collected, the tumor (111)In and (177)Lu activity concentration determined, and tumor regression/cell density was recorded. RESULTS: In animals given curative amounts, the uptake of (111)In was lower than in untreated animals. On the other hand, a second late injection (3-13 days) after suboptimal amounts resulted in a twofold higher tumor activity concentration versus untreated animals. When the uptake of the curative injection was corrected for tumor cell density, which decreased from 66% to 4% over 2 weeks, an enhanced uptake per tumor cell was observed. The curative and suboptimal amounts resulted in a different uptake and retention of (177)Lu in tumors. The suboptimal amount resulted in a constant activity concentration, while the curative amount resulted in an increased activity concentration over time. CONCLUSIONS: Our results, as presented in this paper, describe how the second injection in a fractionation protocol will be affected by the first therapeutic amount. This new information might be useful in the optimization of radionuclide therapy.
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| 19. |
- Bäcktorp, Carina, 1964, et al.
(författare)
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Mechanisms of Air Oxidation of Ethoxylated Surfactants - Computational Estimations of Energies and Reaction Behaviors
- 2008
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 14:31, s. 9549-9554
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Tidskriftsartikel (refereegranskat)abstract
- Pathways for formation of previously observed autoxidation products of ethoxylated surfactants have been studied by DFT (B3LYP). In addition to the established radical-chain reaction, several mechanistic possibilities for intramolecular fragmentation of the intermediate radicals have been characterized concerning reaction barriers and energies of transition states. The results can rationalize the formation of previously observed autoxidation products, including several, which have been implicated as strongly allergenic.
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| 20. |
- Dindelegan, G., et al.
(författare)
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Accelerated acute rejection of the intestinal graft in CD28-deficient mice.
- 2007
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 37:1, s. 82-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Multiple in vivo studies have shown that the pace and severity of graft rejection is little or not at all changed by deleting CD28 molecules in the recipient. These findings contrast with the effects of monoclonal antibody therapy aimed the same costimulatory target. The objective of the present study was to evaluate how the acute rejection process is affected in CD28-deficient mice using a fully allogeneic, highly immunologically reactive transplant model. METHODS: Heterotopic vascularized small bowel transplants were performed in 24 recipient mice divided into 4 groups: 2 wild-type and 2 knockout groups. Each group consisted of 5 to 7 animals in which BalbC mice were used as intestinal donors to either wild-type C57BL6 or C57BL6 background CD28-deficient recipient mice. Selected endpoints were 3 and 6 postoperative days (POD). Intestinal rejection was evaluated by mucosal laser Doppler flowmetry (expressed in perfusion units) and histology (expressed in rejection grades). RESULTS: Acute rejection occurred in both wild-type and CD28-deficient groups. At POD 3, no significant difference was noted between groups in terms of mucosal perfusion and histology. At POD 6, significant differences in graft mucosal perfusion and histology revealed a more aggressive rejection in the CD28-deficient group compared to the wild-type group. CONCLUSIONS: The present study showed that the severity of intestinal graft rejection responses was amplified by deleting CD28 molecules. Together with data from other studies, these results suggest a different pattern of distribution and/or activation of CD28/B7 receptors in various organs.
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| 21. |
- Forssell-Aronsson, Eva, 1961, et al.
(författare)
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Aspects on radionuclide therapy in malignant pheochromocytomas.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- Malignant pheochromocytomas/paragangliomas (PCs/PGs) often have distant metastases to the skeleton, liver, and lungs. Radionuclide therapy is valuable for treatment of disseminated tumor disease and could be used as adjuvant therapy after surgery. Patients with local and/or distant metastases of PC/PG should be investigated preoperatively by scintigraphy using both 123I-MIBG and 111In-DTPA-D-Phe1-octreotide, to evaluate the possibilities for radionuclide therapy (i.e., a dosimetric estimation of radiation dose to the tumor tissue versus critical normal tissues). Individual patient dose-planning should be performed. For patients in whom positive therapeutic effects are anticipated radionuclide therapy can be applied. Therapy with both 131I-MIBG and 177Lu-octreotate might be favorable in individual patients with lesions visualized by both metaiodobenzylguanidine (MIBG) and octreotide scintigraphy with enhanced therapeutic effects and reduced side effects.
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| 22. |
- Jansson, Svante, 1948, et al.
(författare)
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Treatment of bilateral pheochromocytoma and adrenal medullary hyperplasia.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 429-35
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Tidskriftsartikel (refereegranskat)abstract
- The risk for bilateral tumors and long-term outcome after conservative cortical-sparing adrenal surgery was studied in a consecutive single-center series. One hundred fifty-four patients were operated on (1950-2004) for pheochromocytoma (PC=137), or abdominal paraganglioma (PG=17). Twenty had MEN 2 (16 MEN 2A; 4 MEN 2B), 15 von Recklinghausen's disease (VRD), and 1 von Hippel-Lindau (VHL) disease. Twelve patients had, or developed, bilateral adrenal medullary tumors; four with MEN 2A, four with MEN 2B, three with VRD, and one with probably hereditary PC associated with brain tumors/meningioma. Two patients with MEN 2B and one with MEN 2A with had bilateral adrenalectomy (adx). Three VRD patients, two MEN 2B and one MEN 2A patients had cortical-sparing surgery. Two patients were operated on unilaterally, but developed small contralateral tumors; one of these (MEN 2A) had a second asymptomatic PC diagnosed at an older age, so surgery was withheld; the other patient (hereditary PC syndrome) had a small contralateral PC diagnosed at autopsy 9 years later. Only three of nine patients with bilateral operations needed corticosteroid replacement after surgery. Four of six patients died of associated tumors (MTC and meningioma). The mean follow-up was 13 (1-25) years. Twelve MEN 2A patients with unilateral adx have been followed up for 20 (4-36) years without developing a second PC. Cortical-sparing adrenal surgery can safely be performed in the majority of patients with bilateral PC. On the basis of our long-term experience of MEN 2A we perform contralateral adrenal resection only if a second PC is confirmed. Five patients underwent adrenal exploration because of clinical and biochemical findings compatible with PC. Four had asymmetrical positive MIBG scans. They all underwent unilateral adx and diffuse medullary hyperplasia was confirmed (medullary weight estimated morphometrically to 1.0-3.4 g vs. normal weight 0.3-0.5 g in matched controls). These patients have been followed for 19 (5-27) years with normal clinical and biochemical findings. In this rare condition removal of the largest adrenal seems adequate.
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| 23. |
- Johanson, Viktor, 1958, et al.
(författare)
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A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis
- 2007
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 14:2, s. 433-444
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET proto-oncogene, resulting in constitutive activation of the RET tyrosine kinase. A substantial proportion of sporadic MTCs also have RET mutations, making the RET tyrosine kinase a potential therapeutic target in MTC. We have established a transplantable MTC in nude mice from a sporadic human MTC carrying a RET C634R mutation. Transplanted tumors had an exponential growth rate with an approximate doubling time of about 3 weeks, and expressed a neuroendocrine phenotype characteristic of MTC, e.g., expression of calcitonin, chromogranin A (CgA), synaptophysin, synaptic vesicle protein 2 (SV2), vesicular monoamine transporter-1 and -2, carcinoembryonic antigen, cytokeratin 8/18, epithelial cadherin, and neural cell adhesion molecule. Plasma calcitonin and CgA levels were elevated in tumor-bearing mice and correlated with tumor size. Cytogenetic analysis, including spectral karyotyping, confirmed the human origin of the xenografted tumors and demonstrated an abnormal, near triploid karyotype. Treatment of tumor-bearing nude mice with the tyrosine kinase inhibitor ZD6474, which specifically inhibits RET, epidermal growth factor receptor (EGFR), and vascular endothelium growth factor receptor (VEGFR) tyrosine kinases, resulted in a dose-dependent inhibition of tumor growth. Oral ZD6474 given once daily (250 mg/kg, 5 days/week) reduced tumor volume to 11% when compared with controls after 4 weeks. Our results show that this transplantable MTC, designated GOT2, represents a novel and useful model for studies of MTC and RET tyrosine kinase-dependent tumor growth.
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| 24. |
- Johanson, Viktor, 1958, et al.
(författare)
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Antitumoural effects of the pyridyl cyanoguanidine CHS 828 on three different types of neuroendocrine tumours xenografted to nude mice
- 2005
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 82:3-4, s. 171-6
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Tidskriftsartikel (refereegranskat)abstract
- CHS 828, a cyanoguanidine with potent experimental antitumoural activity, inhibits activation of nuclear factor-kappaB. In the present study, marked antitumoural activity of peroral CHS 828 was shown against three different human neuroendocrine tumours, midgut carcinoid (GOT1), pancreatic carcinoid (BON), and medullary thyroid carcinoma (GOT2), transplanted in nude mice. Our results indicate that CHS 828 can be a candidate drug for treatment of neuroendocrine tumours.
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| 25. |
- Khorram-Manesh, Amir, 1958, et al.
(författare)
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Mortality associated with pheochromocytoma: increased risk for additional tumors.
- 2006
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923. ; 1073, s. 444-8
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Tidskriftsartikel (refereegranskat)abstract
- A consecutive series of patients (68 females and 53 males) with pheochromocytoma (PC, n=110) or paraganglioma (PG, n=11) were treated at the Sahlgrenska University Hospital (1950-1997). During the observation period (15+/-6 years) 42 patients died versus 23.6 expected in the general population (P<0.001). There was no surgical mortality. Twenty patients died of cardiovascular disease, 11 of other tumors, and 7 of other diseases, but only 4 of PC/PG. The main causes of death in this regional series were cardiovascular diseases and tumor in a ratio of 1.3 versus 2.0 in the general Swedish population. Analysis of the mortality in all patients with clinically diagnosed PC (n=481, 259 women and 222 men) based on the National Cancer Registry (1957-1997) showed that the number of deaths in this cohort was 196 versus 153.4 expected (P<0.001). These patients had almost four times higher risk of dying of a tumor than did the general population (similar risk for females and males). There was no increased risk for cardiovascular death; in fact, the risk was lower than expected for men (22 vs. 38 expected). A second tumor diagnosed subsequent to PC occurred in 68 versus 31 expected. In men tumors of the liver and biliary tract and central nervous system and in women malignant melanoma and cervix carcinoma were most frequent. The results from the national series thus confirm an increased risk of a second tumor and increased tumor-related mortality in patients with PC.
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