| 21. |
- Nilsson, Bengt E, 1949, et al.
(author)
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Treatment of gastrointestinal stromal tumours: imatinib, sunitinib -- and then?
- 2009
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In: Expert opinion on investigational drugs. - : Informa Healthcare. - 1744-7658 .- 1354-3784. ; 18:4, s. 457-68
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Journal article (peer-reviewed)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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| 22. |
- Nyberg, Jenny, 1976, et al.
(author)
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Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation.
- 2005
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In: 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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Journal article (peer-reviewed)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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| 23. |
- Størsrud, Stine, 1972, et al.
(author)
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Adult coeliac patients do tolerate large amounts of oats.
- 2003
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In: European journal of clinical nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 57:1, s. 163-9
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Journal article (peer-reviewed)abstract
- The aim of the present study was to investigate whether adult patients with coeliac disease in remission could include large amounts of oats in their daily gluten-free diet for an extended period of time without adverse effects. DESIGN, SUBJECTS AND METHODS: Twenty adult coeliac patients in remission included large amounts of uncontaminated rolled oats in their daily diet for a prolonged period. The examinations, performed four times during the study period, included small bowel endoscopy with biopsies, blood samples (nutritional status, serological analysis), height and body weight, gastrointestinal symptoms and dietary records. Gastrointestinal symptoms and diet were also investigated through unannounced telephone interviews once a month during the study period.
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| 24. |
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| 25. |
- Wängberg, Bo, 1953, et al.
(author)
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The long-term survival in adrenocortical carcinoma with active surgical management and use of monitored mitotane.
- 2010
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In: Endocrine-related cancer. - 1479-6821. ; 17:1, s. 265-72
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Journal article (peer-reviewed)abstract
- Adrenocortical carcinoma (ACC) is a rare tumour disease with sinister prognosis also after attempts to radical surgery; better prognosis is seen for low-stage tumours. Adjuvant treatment with the adrenolytic drug mitotane has been attempted, but not proven to prevent from recurrence. The drug may offer survival advantage in case of recurrence. The aim of this single-centre study (1979-2007) of 43 consecutive patients was to evaluate the long-term survival after active surgical treatment combined with monitored mitotane (to reduce side effects of the drug). The series is unique, since all patients were offered a period of mitotane as adjuvant or palliative treatment; six patients refused mitotane. Despite a high proportion of high-stage tumours (67%), the complete resection rate was high (77%). The disease-specific 5-year survival was high (64.1%); very high for patients with low-stage tumours without evident relation to mitotane levels. Patients with high-stage tumours had a clear survival advantage with mitotane levels above a threshold of 14 mg/l in serum. The hazard ratio for patients with high mitotane levels versus all patients indicates a significant effect of the drug. The results indicate that adjuvant mitotane may be the standard of care for patients with high-stage ACC after complete resection.
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| 26. |
- Abrahamsson, Jonas, 1954, et al.
(author)
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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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In: Journal of pediatric surgery. - : Elsevier BV. - 1531-5037 .- 0022-3468. ; 40:11
-
Journal article (peer-reviewed)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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| 27. |
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| 28. |
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| 29. |
- Ahlman, Håkan, 1947, et al.
(author)
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Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.
- 1994
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In: The British journal of surgery. - 0007-1323. ; 81:8, s. 1144-9
-
Journal article (peer-reviewed)abstract
- 111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.
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| 30. |
- Ahlman, Håkan, 1947, et al.
(author)
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Clinical management of gastric carcinoid tumors.
- 1994
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In: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
-
Journal article (peer-reviewed)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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