| 31. |
- Costa, F., et al.
(författare)
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Management of neuroendocrine tumors : a meeting of experts from Latin America
- 2008
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 88:3, s. 235-42
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Tidskriftsartikel (refereegranskat)abstract
- A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.
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| 32. |
- Crona, Joakim, et al.
(författare)
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Effect of Temozolomide in Patients with Metastatic Bronchial Carcinoids
- 2013
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 98:2, s. 151-155
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Metastatic bronchial carcinoids are rare neoplasms, where efforts of medical treatment so far have been disappointing. A previous study from our center indicated that temozolomide might be of value. Materials and Methods: All patients with progressive metastatic bronchial carcinoid treated with tennozolomide as monotherapy at our center between 2004 and 2010 (n = 31) were included in this retrospective study. 14 tumors were classified as typical and 15 as atypical carcinoids, whereas 2 tumors could not be classified. Temozolomide was given on 5 consecutive days every 4 weeks. Toxicity was evaluable in 28 of 31 patients, and 22 patients were evaluable by RECIST 1.1. Results: There were no complete responses. A partial response was seen in 3 patients (14%), stable disease in 11(52%) and progressive disease in 7 patients (33%). Median progression-free survival was 5.3 months and median overall survival was 23.2 months from the start of temozolomide. Toxcities grade 3-4 were noted in 4 patients, thrombocytopenia (n =3) and leukopenia (n = 1). Conclusion: Temozolomide as monotherapy shows activity in metastatic bronchial carcinoids. Regimens combining tennozolomide with other agents (e.g. capecitabine and/or bevacizumab, everolimus, radiolabeled somatostatin analogues) should be further studied in these patients. Copyright (C) 2013 S. Karger AG, Basel
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Csoregh, L, et al.
(författare)
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Transcriptional analysis of estrogen effects in human embryonic neurons and glial cells
- 2009
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 1423-0194 .- 0028-3835. ; 89:2, s. 171-186
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen exerts many effects in the central nervous system which extend beyond regulating sexual behavior and gonadal function in reproduction. It has been shown that estrogen has a range of both neuroprotective and neuromodulatory effects, but little is known about the molecular mechanisms underlying estrogen actions in the human brain. We therefore analyzed the transcriptional response to estrogen by microarray technology in primary cell cultures of neurons and glial cells derived from 8- to 12-week human fetal brain tissue. Estrogen treatment of the cell cultures during a 7-day culture period revealed a number of genes with significantly altered expression. Fourteen genes were selected for further analysis by quantitative real-time PCR in order to confirm the gene expression changes observed by the microarray analysis. Six genes were identified with important roles in the nervous system that have not been described before to be estrogen-regulated. Three genes, IGFBP7, Transgelin and Cyr61, were further analyzed by immunostaining, and were found to be expressed in both primary neurons and glial cells. Our results indicate that estrogen may influence developing human neurons and glia through regulating expression of genes that are important for the development of the nervous system.
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| 37. |
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| 38. |
- Dam, Gitte, et al.
(författare)
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Prospective Study of Chromogranin A as a Predictor of Progression in Patients with Pancreatic, Small-Intestinal, and Unknown Primary Neuroendocrine Tumors
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 110:3/4, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Background: Retrospective studies are conflicting but most of them report that an increase in plasma chromogranin A (CgA) predicts tumor progression in neuroendocrine tumor (NET) patients. Prospectively, we investigated if a change in plasma CgA is associated with tumor burden changes in NET patients with disseminated disease. Methods: We included 239 patients treated at 5 NET centers from December 2010 to December 2013. CgA was measured within 6 weeks of a CT or MRI in a patient undergoing at least 2 scan examinations performed over a period of 1-24 months. In a post hoc analysis, CgA measured 3-6 months prior to the CT/MRI was analyzed. Changes in tumor size were evaluated by RECIST1.1. A 25% change in CgA was chosen to discriminate between increased, decreased, or unchanged levels. Results: In 671 events (2 CT/MRI scans and 2 corresponding CgA measurements), we found a weak positive correlation between the RECIST 1.1 responses and change in plasma CgA from baseline (Spearman's rank correlation coefficient: 0.15; p < 0.05). Of 304 events in the post hoc analysis, 58 showed progression, 228 showed stable disease, and 18 showed regression, with a median change in CgA of 19% (IQR: 57 to -20%), -12% (23 to -38%), and -73% (-55 to -83%), respectively. The correlation coefficient for all sites was 0.17 (p = 0.003), and it was 0.16 (p = 0.07), 0.18 (p = 0.04), and 0.20 (p = 0.21) for small-intestinal (n = 137), pancreatic (n = 123), and unknown primary NET (n = 40), respectively. In the 58 patients showing tumor progression, the sensitivity and specificity of an increased CgA concentration were 36 and 82%, respectively, with positive and negative predictive values of 32 and 85%. Conclusions: In this prospective study of gastroenteropancreatic NET patients, we observed only a weak association between a change in plasma CgA and changes in tumor burden. CgA as a single biomarker was thus inadequate to predict tumor progression.
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| 39. |
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| 40. |
- Daskalakis, Kosmas, 1979-, et al.
(författare)
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Increased Autophagy/Mitophagy Levels in Pancreatic Neuroendocrine Neoplasms
- 2020
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 110:Suppl. 1, s. 7-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Autophagy and mitophagy are key homeostatic machineries linked to cancer development and drug resistance.Aim(s): To assess the levels of autophagy and mitophagy in well differentiated pancreatic neuroendocrine neoplasms (PanNENs) and correlate them with clinico-pathological parameters. Materials and methods: Fluorescent immunostaining for the autophagy markers LC3 Βand p62/or LAMP1 was performed on 22 PanNENs and 11 controls of normal pancreatic tissues and validated through Western blotting. Autophagy quantitative scoring was generated for LC3B-positive puncta and analyzed in relation to clinico-pathological parameters. TOMM20/LC3B qualitative assessment of mitophagy levels was undertaken by fluorescent immunostaining. The presence of autophagy/mitophagy was validated by transmission electron microscopy.Results: Autophagy levels (LC3B-positive puncta/cell) were discriminative for normal vs. NEN pancreatic tissue (p=0.007). A significant association was observed between autophagy levels and tumour grade (Ki67<3% vs. Ki67≥3%; p=0.021), but not functionality (p=0.266) size (cut-off of 20mm; p=0.808), local invasion (p=0.481), lymph node- (p=0.849) and distant metastases (p=0.699). Qualitative assessment of TOMM20/LC3B demonstrated strong mitophagy levels in PanNENs by fluorescent immunostaining as compared to normal tissue. Transmission electron microscopy revealed enhanced autophagy and mitophagy in PanNEN tissue. Response to molecular targeted therapies in metastatic cases (n=4) did not reveal any patterns of association to autophagy levels.Conclusion: Increased autophagy levels are present in primary tumours of patients with PanNENs and are partially attributed to upregulated mitophagy. Grade was the only clinico-pathological parameter associated with autophagy scores.
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