scholarly journals Deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development

Oncogene ◽  
2011 ◽  
Vol 31 (11) ◽  
pp. 1459-1467 ◽  
Author(s):  
S M Pyonteck ◽  
B B Gadea ◽  
H-W Wang ◽  
V Gocheva ◽  
K E Hunter ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neuroendocrine Tumor ◽  
Tumor Development ◽  
Pancreatic Neuroendocrine Tumor

Activity of Sunitinib in Patients With Advanced Neuroendocrine Tumors

2008 ◽  
Vol 26 (20) ◽  
pp. 3403-3410 ◽  
Author(s):  
Matthew H. Kulke ◽  
Heinz-Josef Lenz ◽  
Neal J. Meropol ◽  
James Posey ◽  
David P. Ryan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Neuroendocrine Tumor ◽  
Neuroendocrine Tumors ◽  
Objective Response ◽  
Pancreatic Neuroendocrine Tumor ◽  
Endocrine Tumor ◽  
Pancreatic Endocrine Tumor ◽  
Tumor Patients ◽  
Patient Reported

Purpose Standard cytotoxic chemotherapy has limited efficacy in metastatic neuroendocrine tumor patients. Neuroendocrine tumors express vascular endothelial growth factor (VEGF) and its receptor (VEGFR). Sunitinib malate, an oral tyrosine kinase inhibitor, has activity against VEGFRs as well as platelet-derived growth factor receptors, stem-cell factor receptor, glial cell line–derived neurotrophic factor, and FMS-like tyrosine kinase-3. We evaluated the efficacy of sunitinib in a two-cohort, phase II study of advanced carcinoid and pancreatic neuroendocrine tumor patients. Patients and Methods Patients were treated with repeated 6-week cycles of oral sunitinib (50 mg/d for 4 weeks, followed by 2 weeks off treatment). Patients were observed for response, survival, and adverse events. Patient-reported outcomes were assessed. Results Among 109 enrolled patients, 107 received sunitinib (carcinoid, n = 41; pancreatic endocrine tumor, n = 66). Overall objective response rate (ORR) in pancreatic endocrine tumor patients was 16.7% (11 of 66 patients), and 68% (45 of 66 patients) had stable disease (SD). Among carcinoid patients, ORR was 2.4% (one of 41 patients), and 83% (34 of 41 patients) had SD. Median time to tumor progression was 7.7 months in pancreatic neuroendocrine tumor patients and 10.2 months in carcinoid patients. One-year survival rate was 81.1% in pancreatic neuroendocrine tumor patients and 83.4% in carcinoid patients. No significant differences from baseline in patient-reported quality of life or fatigue were observed during treatment. Conclusion Sunitinib has antitumor activity in pancreatic neuroendocrine tumors; its activity against carcinoid tumors could not be definitively determined in this nonrandomized study. Randomized trials of sunitinib in patients with neuroendocrine tumors are warranted.

scholarly journals 24-Hydroxycholesterol participates in pancreatic neuroendocrine tumor development

2016 ◽  
Vol 113 (41) ◽  
pp. E6219-E6227 ◽  
Author(s):  
Matias Soncini ◽  
Gianfranca Corna ◽  
Marta Moresco ◽  
Nadia Coltella ◽  
Umberto Restuccia ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Tumor Development ◽  
Pancreatic Neuroendocrine Tumor ◽  
Tumor Diameter ◽  
Angiogenic Switch ◽  
Tumor Microenvironments ◽  
Oxidized Products ◽  
Protumoral Activities

Cells in the tumor microenvironment may be reprogrammed by tumor-derived metabolites. Cholesterol-oxidized products, namely oxysterols, have been shown to favor tumor growth directly by promoting tumor cell growth and indirectly by dampening antitumor immune responses. However, the cellular and molecular mechanisms governing oxysterol generation within tumor microenvironments remain elusive. We recently showed that tumor-derived oxysterols recruit neutrophils endowed with protumoral activities, such as neoangiogenesis. Here, we show that hypoxia inducible factor-1a (HIF-1α) controls the overexpression of the enzyme Cyp46a1, which generates the oxysterol 24-hydroxycholesterol (24S-HC) in a pancreatic neuroendocrine tumor (pNET) model commonly used to study neoangiogenesis. The activation of the HIF-1α–24S-HC axis ultimately leads to the induction of the angiogenic switch through the positioning of proangiogenic neutrophils in proximity to Cyp46a1+ islets. Pharmacologic blockade or genetic inactivation of oxysterols controls pNET tumorigenesis by dampening the 24S-HC–neutrophil axis. Finally, we show that in some human pNET samples Cyp46a1 transcripts are overexpressed, which correlate with the HIF-1α target VEGF and with tumor diameter. This study reveals a layer in the angiogenic switch of pNETs and identifies a therapeutic target for pNET patients.

Case report: Refractory hypercalcemia due to a pancreatic neuroendocrine tumor misdiagnosed as adenocarcinoma

2020 ◽  
Author(s):  
Mirella Hage ◽  
Ségolène Hescot ◽  
Amani Asnacios ◽  
Sophia Bakopoulou ◽  
Laure Cazabat ◽  
...  
Keyword(s):  
Case Report ◽  
Neuroendocrine Tumor ◽  
Pancreatic Neuroendocrine Tumor

scholarly journals Heterogeneity of the Clinical Presentation of the MEN1 LRG_509 c.781C>T (p.Leu261Phe) Variant Within a Three-Generation Family

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 512
Author(s):  
Aleksandra Gilis-Januszewska ◽  
Anna Bogusławska ◽  
Kornelia Hasse-Lazar ◽  
Beata Jurecka-Lubieniecka ◽  
Barbara Jarząb ◽  
...  
Keyword(s):  
Neuroendocrine Tumor ◽  
Clinical Presentation ◽  
Age Of Onset ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Family Members ◽  
Pancreatic Neuroendocrine Tumor ◽  
Index Patient ◽  
Generation Family

Multiple neuroendocrine neoplasia type 1 (MEN1) is a rare genetic disorder with an autosomal dominant inheritance, predisposing carriers to benign and malignant tumors. The phenotype of MEN1 syndrome varies between patients in terms of tumor localization, age of onset, and clinical aggressiveness, even between affected members within the same family. We describe a heterogenic phenotype of the MEN1 variant c.781C>T (LRG_509t1), which was previously reported only once in a family with isolated hyperparathyroidism. A heterozygous missense variant in exon 4 of the gene was identified in the sequence of the MEN1 gene, i.e., c.781C>T, leading to the amino acid change p.Leu261Phe in a three-generation family. In the screened family, 5/6 affected members had already developed hyperparathyroidism. In the index patient and two other family members, an aggressive course of pancreatic neuroendocrine tumor (insulinoma and non-functioning neuroendocrine tumors) with dissemination was diagnosed. In the index patient, late diagnosis and slow progression of the disseminated neuroendocrine tumor have been observed (24 years of follow-up). The very rare variant of MEN1, LRG_509t1 c.781C>T /p.Leu261Phe (LRG_509p1), diagnosed within a three-generation family has a heterogenic clinical presentation. Further follow-up of the family members should be carried out to confirm the spectrum and exact time of clinical presentation.

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