Significance of TNF-α and IL-6 expression in invasive pituitary adenomas

Wu, Junlu; Qiao, Junbo; Duan, Qianglin

doi:10.4238/gmr.15017502

Cited by 12 publications

(13 citation statements)

References 13 publications

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“…This is so because mirtazapine [23] and quetiapine [24] decrease the antidepressant actions associated with tumor necrosis factor-α (TNF-α). TNF-α level is increased in invasive pituitary adenomas [25] such as the one diagnosed in our patient. However, increased TNF-α associated with the metabolic syndrome and use of quetiapine has been reported [26].…”

Section: Discussionmentioning

confidence: 65%

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report

Casulari

Castro

Kessler³

et al. 2019

J Med Case Reports

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Background Prolactinomas are tumors of the pituitary gland that usually respond very well to treatment with cabergoline. Resistance to cabergoline is very rare, but when it occurs, it is a difficult problem to resolve if the tumor is inoperable. Case presentation A 62-year-old white man was treated for a giant macroprolactinoma detected during investigation of a subacute subdural hematoma of the left frontal lobe. The patient was treated with cabergoline for 17 years with a dose ranging from 1.0 mg to 3.5 mg per week. We were not able to normalize his prolactin level, which initially was 14,992 ng/ml and ultimately 1754 ng/ml. The tumor significantly shrank during the follow-up period but persisted. The patient had cardiac valvulopathies that did not worsen. He had an ischemic stroke and developed a psychotic condition that was successfully treated by lowering the cabergoline and administering quetiapine and mirtazapine together. This regimen led to a small increase in the patient’s prolactin that returned to previous levels and remained as such until the last medical evaluation. The tumor continued to shrink and had a cystic degeneration in the last evaluation. Conclusions Combined use of cabergoline with quetiapine and mirtazapine to treat a psychotic crisis may have contributed to shrinking the tumor in our patient because these antipsychotics have action mediated by growth factors that interfere with growth of pituitary tumors.

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Section: Discussionmentioning

confidence: 65%

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report

Casulari

Castro

Kessler³

et al. 2019

J Med Case Reports

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“…A study involving 40 cases each of invasive pituitary adenoma (IPA) and non-invasive pituitary adenoma (NIPA) used the streptavidin peroxidase immunohistochemical method to examine TNF-α and IL-6 expression. The study found that both TNF-α and IL-6 were more highly expressed in IPA tissues than in NIPA, highlighting their significant roles in IPA development and progression [57].…”

Section: Exploring the Microenvironment's Contribution To Pituitary A...mentioning

confidence: 83%

From Genes to Therapy: Pituitary Adenomas in the Era of Precision Medicine

Toader,

Dobrin,

Tataru

et al. 2023

Biomedicines

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This review presents a comprehensive analysis of pituitary adenomas, a type of brain tumor with diverse behaviors and complexities. We cover various treatment approaches, including surgery, radiotherapy, chemotherapy, and their integration with newer treatments. Key to the discussion is the role of biomarkers in oncology for risk assessment, diagnosis, prognosis, and the monitoring of pituitary adenomas. We highlight advances in genomic, epigenomic, and transcriptomic analyses and their contributions to understanding the pathogenesis and molecular pathology of these tumors. Special attention is given to the molecular mechanisms, including the impact of epigenetic factors like histone modifications, DNA methylation, and transcriptomic changes on different subtypes of pituitary adenomas. The importance of the tumor immune microenvironment in tumor behavior and treatment response is thoroughly analyzed. We highlight potential breakthroughs and innovations for a more effective management and treatment of pituitary adenomas, while shedding light on the ongoing need for research and development in this field to translate scientific knowledge into clinical advancements, aiming to improve patient outcomes.

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“…IL-6 plays a role in progression and aggressiveness of PitNETs (Jones et al 1994, Velkeniers et al 1994, Arzt et al 1999, Kurotani et al 2001, Haedo et al 2009. Invasive PitNETs have a high proportion of IL-6 expression (67.5%), while non-invasive PitNETs expressed IL-6 only in 22.5% of cases (Wu et al 2016). Suppression of…”

Section: Discussionmentioning

confidence: 99%

Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness

Marques

Barry

Carlsen³

et al. 2019

Endocrine-Related Cancer

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Tumour-associated fibroblasts (TAFs) are key elements of the tumour microenvironment, but their role in pituitary neuroendocrine tumours (PitNETs) has been little explored. We hypothesised that TAF-derived cytokines may play a role in tumour aggressiveness and that their release can be inhibited by somatostatin analogues. TAFs were isolated and cultured from 16 PitNETs (11 clinically non-functioning tumours and 5 somatotropinomas). The fibroblast secretome was assessed with a 42-plex cytokine array before and after multiligand somatostatin receptor agonist pasireotide treatment. Angiogenesis and epithelial-to-mesenchymal transition pathway assessment included CD31, E-cadherin and ZEB1 expression. GH3 cells treated with TAF- or skin fibroblast-conditioned medium were assessed for migration, invasion and cell morphology changes. PitNET TAFs secreted significant amounts of cytokines including CCL2, CCL11, VEGF-A, CCL22, IL-6, FGF-2 and IL-8. TAFs from PitNETs with cavernous sinus invasion secreted higher IL-6 levels compared to fibroblasts from non-invasive tumours (P = 0.027). Higher CCL2 release from TAFs correlated with more capillaries (r = 0.672, P = 0.004), and TAFs from PitNETs with a higher Ki-67 tended to secrete more CCL2 (P = 0.058). SST1 is the predominant somatostatin receptor in TAFs, and pasireotide decreased TAF-derived IL-6 by 80% (P < 0.001) and CCL2 by 35% (P = 0.038). GH3 cells treated with TAF-conditioned medium showed increased migration and invasion compared to cells treated with skin fibroblast-conditioned medium, with morphological and E-cadherin and ZEB1 expression changes suggesting epithelial-to-mesenchymal transition. TAF-derived cytokines may increase PitNET aggressiveness, alter angiogenesis and induce epithelial-to-mesenchymal transition changes. Pasireotide’s inhibitory effect on TAF-derived cytokines suggest that this effect may play a role in its anti-tumour effects.

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Significance of TNF-α and IL-6 expression in invasive pituitary adenomas

Cited by 12 publications

References 13 publications

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report

Giant cabergoline-resistant prolactinoma in a man who presented with a psychotic episode during treatment: a case report

From Genes to Therapy: Pituitary Adenomas in the Era of Precision Medicine

Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness

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