Pancreatic neuroendocrine tumors

Karakaxas, Dimitrios; Gazouli, Maria; Liakakos, Theodore; Vaiopoulou, Anna; Apessou, Dimitra; Papaparaskeva, Kleo; Patapis, Paul; Dervenis, Christos

doi:10.1097/meg.0000000000000138

Cited by 9 publications

(2 citation statements)

References 123 publications

(147 reference statements)

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“…Traditional chemotherapy is generally ineffective and patient management often encompasses only symptom palliation. 20 Previous studies demonstrated RBP2 overexpression in non-NETs; 19 however, we are the first group to show overexpression of RBP2 in NETs and their metastases. In this study, we identified and quantified RBP2 overexpression in 20 out of 25 human NET samples, or 80% of the tumors measured.…”

Section: Discussionmentioning

confidence: 72%

Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype

et al. 2016

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Neuroendocrine tumors (NETs), which can have survival rates as low as 4%, currently have limited therapeutic interventions available highlighting the dire need for the identification of novel biological targets for use as new potential drug targets. One such potential target is retinoblastoma-binding protein 2 (RBP2), an H3K4 demethylase whose overexpression has been linked to cancer formation and metastasis in non-endocrine tumor types. We measured RBP2 mRNA and protein levels in enteropancreatic NETs by measuring RBP2 in matched human normal and NET tissue samples. Further, proliferation, migration, invasion and colony formation assays were performed in the physiologically relevant NET cell lines βlox5, H727 and QGP-1 to understand the role of RBP2 and its demethylase activity on end points of tumorigenesis. Our data indicate a strong correlation between RBP2 mRNA and protein expression in NET specimens. RBP2 was overexpressed relative to tissue-matched normal controls in 80% of the human tumors measured. In vitro studies showed RBP2 overexpression significantly increased proliferation, migration, invasion and colony formation, whereas knockdown significantly decreases the same parameters in a demethylase-independent manner. The cell cycle inhibitors p21 and p57 decreased with RBP2 overexpression and increased upon its depletion, suggesting a regulatory role for RBP2 in cellular proliferation. Taken together, our results support the hypothesis that the aberrant overexpression of RBP2 is a frequent contributing factor to tumor formation and metastasis in enteropancreatic NETs.

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Section: Discussionmentioning

confidence: 72%

Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype

et al. 2016

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“…Surgical resection is the cornerstone of treatment for localised disease [ 7 , 8 ]. The optimum surgical approach or extent of lymphadenectomy however is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic Aetiology for Massive Upper Gastrointestinal Haemorrhage in Pregnancy

Zaborowski

Walsh

Ravi

et al. 2016

Case Reports in Surgery

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We present herein what we believe is the first reported case of massive upper gastrointestinal bleeding in pregnancy due to a pancreatic neuroendocrine tumour causing left sided portal hypertension. A 37-year-old 27-week pregnant female presented with massive haematemesis and melaena requiring transfusion of 10 units of red cell concentrate. Gastric varices were evident at endoscopy. An MRI revealed a large mass infiltrating the pancreatic tail and spleen with massive upper abdominal varix formation secondary to splenic vein invasion. A caesarean section was performed, followed by a radical en bloc partial pancreatectomy and splenectomy with resection of the fundus of the stomach and ligation of gastric and splenic varices. Her postoperative course was uncomplicated. Histology revealed a well differentiated grade 2 neuroendocrine tumour with final staging of T4N0. This case highlights an infrequently encountered cause of massive gastrointestinal bleeding. Diagnosis and management of pancreatic neuroendocrine tumours, due to their rarity and variable clinical presentation, can be challenging particularly in the setting of pregnancy where the wellbeing of a second patient must also be considered. A multidisciplinary approach with input from obstetricians and general surgeons is required when deciding optimum management, while also taking into account the patient's preferences.

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Management of Small Nonfunctional Pancreatic Neuroendocrine Tumors

Grisotti

Khan

2016

Difficult Decisions in Surgery: An Evidence-Based Approach

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Pancreatic neuroendocrine tumors

Cited by 9 publications

References 123 publications

Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype

Retinoblastoma-binding protein 2 (RBP2) is frequently expressed in neuroendocrine tumors and promotes the neoplastic phenotype

Pancreatic Aetiology for Massive Upper Gastrointestinal Haemorrhage in Pregnancy

Management of Small Nonfunctional Pancreatic Neuroendocrine Tumors

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