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- Culler, Michael D., et al.
(författare)
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Somatostatin analogs for the treatment of neuroendocrine tumors
- 2011
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Ingår i: Cancer Metastasis Review. - : Springer Science and Business Media LLC. - 0167-7659 .- 1573-7233. ; 30:1, s. 9-17
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Forskningsöversikt (refereegranskat)abstract
- Somatostatin is an important regulator of endocrine and exocrine secretion, affecting the release of many hormones. The effects of somatostatin are mediated through its interaction with one of five somatostatin receptors. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express multiple somatostatin receptors, making them excellent potential therapeutic targets. Many trials have shown that treatment with somatostatin analogs is associated with disease stabilization and prolonged survival. More recently, somatostatin analogs have been shown to have antiproliferative effects, thus broadening the scope of their uses. In this review, we update the current data on the treatment of GEP-NETs with somatostatin analogs, with particular emphasis on the results of the PROMID study. In addition, we discuss the current state of knowledge of novel therapies against GEP-NETs, including the use of somatostatin analogs with broader receptor binding profiles, chimeric somatostatin-dopamine molecules, combinations of somatostatin analogs with other active chemotherapy agents, and peptide receptor-targeted radionuclide therapy.
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| 2. |
- de Boer, Rudolf A, et al.
(författare)
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The WAP four-disulfide core domain protein HE4 : a novel biomarker for heart failure.
- 2013
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1787 .- 2213-1779. ; 1:2, s. 164-169
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF).BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment.METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization.RESULTS: HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model.CONCLUSIONS: HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
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| 3. |
- Kvols, Larry K, et al.
(författare)
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Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR : results from a phase II study
- 2012
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Ingår i: Endocrine-related cancer. - 1479-6821. ; 19:5, s. 657-66
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Tidskriftsartikel (refereegranskat)abstract
- Pasireotide (SOM230) is a novel multireceptor-targeted somatostatin (sst) analog with high binding affinity for sst receptor subtype 1, 2, 3 (sst(1,2,3)) and sst(5). Because of this binding profile, pasireotide may offer symptom control in patients with neuroendocrine tumors (NETs) and carcinoid syndrome no longer responsive to octreotide LAR. This was a phase II, open-label, multicenter study of pasireotide in patients with advanced NET whose symptoms of carcinoid syndrome (diarrhea/flushing) were inadequately controlled by octreotide LAR. Patients received s.c. pasireotide 150 μg twice daily (bid), escalated to a maximum dose of 1200 μg bid until a clinical response was achieved. Forty-four patients were evaluated for efficacy and 45 for tolerability. Pasireotide 600-900 μg s.c. bid effectively controlled the symptoms of diarrhea and flushing in 27% of patients. Evaluation of tumor response in 23 patients showed 13 with stable disease and ten with progressive disease at study end. The most common drug-related adverse events were nausea (27%), abdominal pain (20%), weight loss (20%), and hyperglycemia (16%) and most were of mild or moderate severity. Pasireotide 600-900 μg s.c. bid was effective and generally well tolerated in controlling the symptoms of carcinoid syndrome in 27% of patients with advanced NET refractory or resistant to octreotide LAR therapy.
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