Effect of hormone secretory syndromes on neuroendocrine tumor prognosis

Zandee, Wouter T; Kamp, Kimberly; Adrichem, Roxanne C van; Feelders, Richard A

doi:10.1530/erc-16-0538

Cited by 46 publications

(44 citation statements)

References 127 publications

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“…The mechanism for the increase in 5-HT levels is unclear, although this phenomenon has been previously observed by Mouillet-Richards in 1C11 cells ( 40 ). A possible explanation might be that dopaminergic and serotonergic cells arise from a common progenitor with a dual biogenic amine fate ( 40 ), which might explain the clinical reports of neuroendocrine tumours in serotoninergic secretion syndromes ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of A549 neuroendocrine differentiation on cytotoxic immune response

Mendieta

Núñez-Anita

Pérez‐Sánchez

et al. 2018

Endocrine Connections

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The present study was designed to determine the effects of factors secreted by the lung adenocarcinoma cell line with the neuroendocrine phenotype, A549NED, on cytotoxic T lymphocytes (CTLs) activity in vitro. A perspective that integrates the nervous, endocrine and immune system in cancer research is essential to understand the complexity of dynamic interactions in tumours. Extensive clinical research suggests that neuroendocrine differentiation (NED) is correlated with worse patient outcomes; however, little is known regarding the effects of neuroendocrine factors on the communication between the immune system and neoplastic cells. The human lung cancer cell line A549 was induced to NED (A549NED) using cAMP-elevating agents. The A549NED cells showed changes in cell morphology, an inhibition of proliferation, an overexpression of chromogranin and a differential pattern of biogenic amine production (decreased dopamine and increased serotonin [5-HT] levels). Using co-cultures to determine the cytolytic CTLs activity on target cells, we showed that the acquisition of NED inhibits the decrease in the viability of the target cells and release of fluorescence. Additionally, the conditioned medium of A549NED and 5-HT considerably decreased the viability and proliferation of the Jurkat cells after 24 h. Thus, our study successfully generated a neuroendocrine phenotype from the A549 cell line. In co-cultures with CTLs, the pattern of secretion by A549NED impaired the proliferation and cytotoxic activity of CTLs, which might be partly explained by the increased release of 5-HT.

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Section: Discussionmentioning

confidence: 99%

Effect of A549 neuroendocrine differentiation on cytotoxic immune response

Mendieta

Núñez-Anita

Pérez‐Sánchez

et al. 2018

Endocrine Connections

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“…SSAs (octreotide, lanreotide, pasireotide) were initially developed to mimic the inhibitory action of somatostatin on cell surface G-protein-coupled receptors called SSTR1–5, which mediate downstream hormone release and cell growth via PI3K and MAPK signaling ( 19 ). These drugs are used successfully to control symptoms of the carcinoid syndrome that is clinically characterized by flushing, diarrhea and right-side heart valve disease as a result of hypersecretion of bioactive amines from small intestinal NETs ( 20 ). The ELECT trial (NCT00774930), a phase III double-blind study of lanreotide depot as a therapy for carcinoid syndrome, enrolled 115 patients—59 in the lanreotide depot arm and 56 in the placebo arm.…”

Section: Target-based Therapies—gastroenteropancreatic Nets (Gep-netsmentioning

confidence: 99%

Clinical and Preclinical Advances in Gastroenteropancreatic Neuroendocrine Tumor Therapy

Crabtree

2017

Front. Endocrinol.

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The molecular events leading to gastroenteropancreatic neuroendocrine tumor (GEP-NET) formation are largely unknown. Over the past decades, systemic chemotherapies have been replaced by therapies directed at particular molecular targets such as the somatostatin receptors, mTOR complexes or proangiogenic molecules. These approaches have demonstrated some success in subtypes of this heterogeneous tumor group, but responses are still widely varied. This review highlights the clinical trials ongoing for neuroendocrine tumors (NETs) and includes emerging immunotherapy, which holds great promise for NETs based on successes in other tumor types. Current avenues of preclinical research, including Notch and PI3K/AKT, will lead to additional targeted therapies based on genome-wide studies that have cast a wide net in the search for driver mutations. Future preclinical and clinical investigations are required to identify those mutations predictive of therapeutic response or disease progression. Results of current clinical trials outlined here will better inform patient management with respect to agent selection, timing, duration and combination therapy in the treatment of NETs.

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“…Patients with GEP NETs can experience numerous and complex symptoms due to the hypersecretion of hormones and peptides such as serotonin, gastrin, insulin, glucagon [5], vasoactive intestinal peptide (VIP) [6], and pancreatic polypeptide [7], which can lead to specific hormonal hypersecretory syndromes. The most prevalent symptoms in patients with GEP NETs include diarrhea, fatigue, abdominal discomfort, flushing, and food intolerance [5].…”

Section: Introductionmentioning

confidence: 99%

Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors

Pusceddu

Rossi

Torchio

et al. 2020

JCM

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Diarrhea is a recurrent symptom in patients with neuroendocrine tumors (NETs) and can represent different etiologies; thus, differential diagnosis is challenging. This paper distinguishes the different causes of chronic diarrhea in patients with gastroenteropancreatic NETs, with the aim to identify the most appropriate therapeutic approach. Underlying causes of diarrhea can be multifactorial, including not only diarrhea that is related to specific hormonal hypersecretory syndromes, but also diarrhea that is secondary to the following: extensive surgery which can cause pancreatic exocrine insufficiency or short bowel syndrome, treatment with somatostatin analogs or other antineoplastic agents, and bile acid malabsorption. After initial management of diarrhea with general treatments (dietary modification, use of antidiarrheals), a proper differential diagnosis is necessary to treat patients with specific etiology-driven therapeutic approaches, such as somatostatin analogs, pancreatic enzyme replacement therapy, and tryptophan hydroxylase inhibitors. In conclusion, NETs should be considered in the differential diagnosis of patients suffering from chronic diarrhea, after the exclusion of more common etiologies. Furthermore, physicians should keep in mind that several different etiologies might be responsible for diarrhea occurrence in NET patients. A prompt diagnosis of the actual cause of diarrhea is necessary to guide the treatment and a multidisciplinary approach is mandatory.

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Effect of hormone secretory syndromes on neuroendocrine tumor prognosis

Cited by 46 publications

References 127 publications

Effect of A549 neuroendocrine differentiation on cytotoxic immune response

Effect of A549 neuroendocrine differentiation on cytotoxic immune response

Clinical and Preclinical Advances in Gastroenteropancreatic Neuroendocrine Tumor Therapy

Differential Diagnosis and Management of Diarrhea in Patients with Neuroendocrine Tumors

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