Treatment of pheochromocytoma blockade of MAPK pathway inhibition in the NF-κB pathway and bFGF — Effect of statins on pheochromocytoma patients

Hu, Heng‐Jing; Zhou, Shenghua; Liu, Qiming

doi:10.1016/j.ijcard.2015.01.005

Cited by 4 publications

(4 citation statements)

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“…After activation, NF-κB can mediate the transcription of various genes, and not only release inflammatory cytokines, but also regulate cell proliferation, apoptosis, morphogenesis and differentiation (37). Blocking the NF-κB pathway can induce apoptosis in chromaffin cells, and NF-κB inhibitors can treat PPGL (38,39). In addition, T cell receptor (TCR) interaction with MHC-antigenic peptide complexes leads to molecular and cellular level changes in T cells, and TCRmediated T cell activation is also closely related to the NF-κB pathway (40,41).…”

Section: Discussionmentioning

confidence: 99%

Biomarker identification of immune-related genes in pheochromocytoma and paraganglioma

Wan¹

2023

Transl Androl Urol

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Background: Although we have a good understanding of the diagnosis and treatment of pheochromocytoma and paraganglioma (PPGL), the underlying pathogenesis and molecular pathways of PPGL need to be further studied. This study aimed to use bioinformatics to analyze the role of immunerelated genes (IRGs) in the pathogenesis of PPGL.Methods: GSE19422 and GSE60459 microarray data were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R, and genes overlapping with IRGs were screened using the "VennDiagram" package. A protein-protein interaction (PPI) network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the core genes were identified by Cytoscape, followed by enrichment analysis and receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic efficacy of the core genes. In addition, the level of immune cell infiltration of PPGL was analyzed and the target drug of the core gene was predicted.Results: A total of 1,105 DEGs were identified from the 2 datasets, of which 94 were IRGs, suggesting that the occurrence of PPGL involved immune-related pathways. Through PPI and Cytoscape, a total of 2 core genes: fibroblast growth factor 2 (FGF2), FYN proto-oncogene (FYN), and vascular cell adhesion molecule 1 (VCAM1) were identified, and the ROC curve showed that these 3 core genes had good efficacy in the diagnosis of PPGL, and more than 50 potential therapeutic drugs could be predicted based on these 3 core genes. Subsequent immunoinfiltration analysis showed that mast cells activated were significantly elevated in patients with PPGL, negatively correlated with macrophages M2, and positively correlated with the level of dendritic cells activated.Conclusions: This study found that immunity is closely related to the occurrence of PPGL, and that FGF2, FYN, and VCAM1 may be potential biomarkers and therapeutic targets of PPGL.

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Section: Discussionmentioning

confidence: 99%

Biomarker identification of immune-related genes in pheochromocytoma and paraganglioma

Wan¹

2023

Transl Androl Urol

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“…Evidence gathered over the last years has prompted an emerging interest in exploring the putative role of statins in the development and progression of different endocrine-and non-endocrine-related tumors [11][12][13][14][15][16], particularly in view of recent meta-analysis analyzing several types of cancer, which revealed that the use of statins improves overall survival and cancer-specific survival [17]. However, to date, the possible antitumor actions of these compounds on PitNETs, as well as the direct effects of statins in normal pituitary cells, had not been reported.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…However, besides their cholesterol-lowering effects, statins have been related with an ample range of pleiotropic effects including immunomodulatory effects triggering the major histocompatibility complex, improvement of endo-thelial function and vasculoprotective effects, alteration of bone metabolism, and so on, [9,10], which confer to statins the ability to affect numerous tissue functions acting through cholesterol-dependent and -independent mechanisms [10]. Importantly, some studies have also related the use of statins with antitumor properties in different endocrine-and non-endocrine-related tumors [11][12][13][14][15][16]. Indeed, a meta-analysis analyzing several types of cancer revealed that the use of statins seems to be beneficial for overall survival and cancer-specific survival [17].…”

Section: Introductionmentioning

confidence: 99%

“…These antitumor effects have been described in several tumor types including, among others, breast cancer, melanoma, and colon cancer [11, 12, 19]. Moreover, statins have been also related with an increase on apoptosis and a reduction on cell proliferation in pheochromocytoma and paraganglioma cells [14, 15], and results recently reported from our group have demonstrated a clear antitumor effect of statins in 2 neuroendocrine tumors-cell models (BON1 and QGP1 cells) [16]. However, to the best of our knowledge, the potential antitumor actions of statins on PitNETs have not been reported to date.…”

Section: Introductionmentioning

confidence: 99%

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Statins Directly Regulate Pituitary Cell Function and Exert Antitumor Effects in Pituitary Tumors

et al. 2020

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Introduction: Pituitary neuroendocrine tumors (PitNETs), the most abundant of all intracranial tumors, entail severe comorbidities. First-line therapy is transsphenoidal surgery, but subsequent pharmacological therapy is often required. Unfortunately, many patients are/become unresponsive to available drugs (somatostatin analogues [SSAs]/dopamine agonists), underscoring the need for new therapies. Statins are well-known drugs commonly prescribed to treat hyper-lipidemia/cardiovascular diseases, but can convey additional beneficial effects, including antitumor actions. The direct effects of statins on normal human pituitary or PitNETs are poorly known. Thus, we aimed to explore the direct effects of statins, especially simvastatin, on key functional parameters in normal and tumoral pituitary cells, and to evaluate the combined effects of simvastatin with metformin (MF) or SSAs. Methods: Effects of statins in cell proliferation/viability, hormone secretion, and signaling pathways were evaluated in normal pituitary cells from a primate model (Papio anubis), tumor cells from corticotropinomas, somatotropinomas, nonfunctioning pituitary tumors, and PitNET celllines (AtT20/GH3-cells). Results: All statins decreased AtT20

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Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons

Modica,

La Salvia,

Liccardi

et al. 2024

Endocrine

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Purpose Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies originating from cells with a neuroendocrine phenotype. The complex relationship between lipid metabolism and cancer is gaining interest and a potential anti-cancer effect of lipid lowering agents is being considered. This review aims to discuss the current understanding and treatment of dyslipidaemia in NENs, focusing on the role of lipid lowering agents, including new therapeutic approaches, and future perspectives as possible tool in cancer prevention and tumor-growth control. Methods We performed an electronic-based search using PubMed updated until December 2023, summarizing the available evidence both in basic and clinical research about lipid lowering agents in NENs. Results Dyslipidemia is an important aspect to be considered in NENs management, although randomized studies specifically addressing this topic are lacking, unlike other cancer types. Available data mainly regard statins, and in vitro studies have demonstrated direct antitumor effects, including antiproliferative effects in some cancers, supporting possible pleiotropic effects also in NENs, but data remain conflicting. Ezetimibe, omega 3-fatty acids, fibrates and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may enhance the regulation of lipid homeostasis, as demonstrated in other cancers. Conclusions Targeting dyslipidemia in NENs should be part of the multidisciplinary management and an integrated approach may be the best option for both metabolic and tumor control. Whether lipid lowering agents may directly contribute to tumor control remains to be confirmed with specific studies, focusing on association with other metabolic risk, disease stage and primary site.

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Treatment of pheochromocytoma blockade of MAPK pathway inhibition in the NF-κB pathway and bFGF — Effect of statins on pheochromocytoma patients

Cited by 4 publications

References 18 publications

Biomarker identification of immune-related genes in pheochromocytoma and paraganglioma

Biomarker identification of immune-related genes in pheochromocytoma and paraganglioma

Statins Directly Regulate Pituitary Cell Function and Exert Antitumor Effects in Pituitary Tumors

Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons

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