ReviewNeuroendocrinology2013
EGFR/TGFα and TGFβ/CTGF Signaling in Neuroendocrine Neoplasia: Theoretical Therapeutic Targets.
Review in Neuroendocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Extracellular signalling regulates gastrin transcription through site-specific phosphorylation and nuclear redistribution of Menin.bioRxiv : the preprint server for biology · 2026Article
- TGFα controls checkpoints in CNS resident and infiltrating immune cells to promote resolution of inflammation.Nature communications · 2025Article
- Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment.International journal of molecular sciences · 2025Review
- The role of cell cycle-related genes in the tumorigenesis of adrenal and thyroid neuroendocrine tumors.Heliyon · 2025Review
- Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.International journal of molecular sciences · 2024Review
- The role of miR-152 in urological tumors: potential biomarkers and therapeutic targets.Frontiers in immunology · 2024Review
- Metastasis and MAPK Pathways.International journal of molecular sciences · 2022Review
- A Report on Multi-Target Anti-Inflammatory Properties of Phytoconstituents fromMolecules (Basel, Switzerland) · 2021Article
- Intracholecystic papillary neoplasm of the gallbladder diagnosed during follow-up of Menetrier's disease: A case report.Molecular and clinical oncology · 2021Article
- Review
- Selective exosome exclusion of miR-375 by glioma cells promotes glioma progression by activating the CTGF-EGFR pathway.Journal of experimental & clinical cancer research : CR · 2021Article
- Transcriptomic Profiling ofFrontiers in oncology · 2021Article
- Epithelial-to-mesenchymal transition markers are differentially expressed in epithelial cancer cell lines after everolimus treatment.Oncology letters · 2020Article
- Pathogenesis and Clinical Management of Mesenteric Fibrosis in Small Intestinal Neuroendocine Neoplasms: A Systematic Review.Journal of clinical medicine · 2020Review
- Identification of new candidate genes and signalling pathways associated with the development of neuroendocrine pancreatic tumours based on next generation sequencing data.Molecular biology reports · 2020Article
- The NETest: The Clinical Utility of Multigene Blood Analysis in the Diagnosis and Management of Neuroendocrine Tumors.Endocrinology and metabolism clinics of North America · 2018Review
- Dexamethasone induced apoptosis of A549 cells via the TGF-β1/Smad2 pathway.Oncology letters · 2018Article
- Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets.Endocrine connections · 2018Review
- Small bowel neuroendocrine tumors: From pathophysiology to clinical approach.World journal of gastrointestinal pathophysiology · 2016Review
- Decoding the Molecular and Mutational Ambiguities of Gastroenteropancreatic Neuroendocrine Neoplasm Pathobiology.Cellular and molecular gastroenterology and hepatology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous family of malignancies whose proliferation is partially dependent on growth factors secreted by the microenvironment and the tumor itself. Growth factors which were demonstrated to be important in experimental models of NENs include EGF (epidermal growth factor), TGF (transforming growth factor) α, TGFβ and CTGF (connective tissue growth factor). EGF and TGFα bind to the EGF receptor to stimulate an intact RAS/RAF/MAPK pathway, leading to the transcription of genes associated with cell proliferation, invasion and metastasis. Theoretically, TGFα stimulation can be inhibited at several points of the MAPK pathway, but success is limited to NEN models and is not evident in the clinical setting. TGFβ1 stimulates TGFβ receptors (TGFβRI and TGFβRII) resulting in inhibition of neuroendocrine cell growth through SMAD-mediated activation of the growth inhibitor P21(WAF1/CIP1). Although some NENs are inhibited by TGFβ1, paradoxical growth is seen in experimental models of gastric and small intestinal (SI) NENs. Therapeutic targeting of TGFβ1 in NENs is therefore complicated by uncertainty of the effect of TGFβ1 secretion on the direction of proliferative regulation. CTGF expression is associated with more malignant clinical phenotypes in a variety of cancers, including NENs. CTGF promotes growth in gastric and SI-NEN models, and is implicated as a mediator of local and distant fibrosis caused by NENs of enterochromaffin cell origin. CTGF inhibitors are available, but their anti-proliferative effect has not been tested in NENs. In summary, growth factors are essential for NEN proliferation, and although interventions targeting these proteins are effective in experimental models, only limited clinical efficacy has been identified.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.