Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review
Abstract
:1. Introduction
2. Experimental Section
3. Results
3.1. Pathogenesis of Mesenteric Fibrosis (MF)
3.1.1. Serotonin
3.1.2. Growth Factors (GFs)
Transforming Growth Factor-β (TGF-β)
Connective Tissue Growth Factor (CTGF)
Platelet-Derived Growth Factor (PDGF)
Insulin-Like Growth Factor 1 (IGF-1)
Epidermal Growth Factor (EGF) and Transforming Growth Factor-a (TGF-α)
Other Growth Factors (GFs)
3.2. Clinical Presentation
Symptoms and Related Deficiencies
3.3. Diagnostic and Classification Systems
3.4. Clinical Management of Mesenteric Fibrosis
3.4.1. Surgical Management
Minimal Invasive Management
3.4.2. Medical Treatment
Somatostatin Analogues (SSAs)
Serotonin Synthesis Inhibitors and 5-HT Receptor Antagonists
Molecular Targeted Therapies (mTOR and Tyrosine Kinase Inhibitors)
Peptide Receptor Radionuclide Therapy (PRRT)
Other Antifibrotic Agents
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Fibrotic Factors | Specific Invovement in MF | Potential Therapeutic Agent Targenting MF | Relevant Studies |
---|---|---|---|
Serotonin | -mitogenic effect in stroma cells -cyclin E induction -potentiates the effects of PDGF, β-FGF, EGF and insulin -decreased expression of serotonin degrading enzymes in the stroma | -SSAs -5-HT synthesis inhibitors and receptor antagonists -Tyrosine kinase inhibitors | [12] [14] [22] [23] [24] [25] [26] [27] |
TGF-β | -chemotactic for fibroblasts and macrophages -cell proliferation -production of extracellular matrix and stimulation of growth factor secretion by fibroblasts | -SSAs -Tyrosine kinase inhibitors -ACE inhibitors -Tamoxifen | [28] [29] [30] [31] [32] [33,34,35] [36] |
CTGF | -promoter of mitosis, chemotaxis -stimulator of apoptosis, angiogenesis, synthesis of collagens, fibronectin and α5-integrin -transcriptional activation through TGF-β1 and other mediators acting in turn as downstream mediator on fibroblasts -SMAD, PKC and ras/MEK/ERK (kinase) pathways necessary for the TGFβ1-mediated induction of the CTGF promoter | -SSAs -Tyrosine kinase inhibitors | [37] [38] [30] [10,39,40,41] |
PDGF | -mitogenic properties on fibroblasts -PDGF a-receptor seen on clusters of tumour cells and occasionally on adjacent stroma -PDGF β -receptor seen only in the stroma -cyclin D1 expression via the MAPK/ERK pathway | -Tyrosine kinase inhibitor (imatinib) | [42] [43] [13] [44] |
IGF-1 | -cell proliferation -mitogenic effect on fibroblasts -serotonin-IGF-1 axis activation | -5-HT synthesis inhibitors and receptor antagonists | [45] [46] [36] [37] [47] [48] |
EGF | -cell proliferation and differentiation -highly expressed in SI-NENs | -Tyrosine kinase inhibitors | [46] |
TGF-α | -interaction with EGF EGFR receptor activation -highly expressed in SI-NENs | -Tyrosine kinase inhibitor | [46] [49] [47] |
FGF | -potent stimulant of endothelial cell growth -cell proliferation and stroma formation | -Tyrosine kinase inhibitors | [12] [28] [36] [43] |
VEGF | -secreted by CAFs to induce tumour cell proliferation | -Tyrosine kinase inhibitors | [46] [50] [6] |
NGF | -regulatory effects on angiogenesis -highly expressed in mesenteric angiopathy | -Tyrosine kinase inhibitors | [36] |
VAP-1 | -higly expressed in SI-NEN stroma | -Pyridazone inhibitors -hVAP-1-targeted inhibitors | [51] [52] |
BMP | -members of the TGF-β superfamily -cell growth and differentiation -promoter of angiopathy | -small molecule inhibitor of BMP signaling, K02288 -Statins | [51] [53] [54,55] |
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Koumarianou, A.; Alexandraki, K.I.; Wallin, G.; Kaltsas, G.; Daskalakis, K. Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review. J. Clin. Med. 2020, 9, 1777. https://doi.org/10.3390/jcm9061777
Koumarianou A, Alexandraki KI, Wallin G, Kaltsas G, Daskalakis K. Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review. Journal of Clinical Medicine. 2020; 9(6):1777. https://doi.org/10.3390/jcm9061777
Chicago/Turabian StyleKoumarianou, Anna, Krystallenia I. Alexandraki, Göran Wallin, Gregory Kaltsas, and Kosmas Daskalakis. 2020. "Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review" Journal of Clinical Medicine 9, no. 6: 1777. https://doi.org/10.3390/jcm9061777