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Frontiers in Oncology 2023Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic... (Review)
Review
Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT.
PubMed: 37823059
DOI: 10.3389/fonc.2023.1254322 -
Journal of Molecular Medicine (Berlin,... Nov 2021The adrenal gland and its hormones regulate numerous fundamental biological processes; however, the impact of hypoxia signaling on adrenal function remains poorly...
The adrenal gland and its hormones regulate numerous fundamental biological processes; however, the impact of hypoxia signaling on adrenal function remains poorly understood. Here, we reveal that deficiency of HIF (hypoxia inducible factors) prolyl hydroxylase domain protein-2 (PHD2) in the adrenal medulla of mice results in HIF2α-mediated reduction in phenylethanolamine N-methyltransferase (PNMT) expression, and consequent reduction in epinephrine synthesis. Simultaneous loss of PHD2 in renal erythropoietin (EPO)-producing cells (REPCs) stimulated HIF2α-driven EPO overproduction, excessive RBC formation (erythrocytosis), and systemic hypoglycemia, which is necessary and sufficient to enhance exocytosis of epinephrine from the adrenal medulla. Based on these results, we propose that the PHD2-HIF2α axis in the adrenal medulla regulates the synthesis of epinephrine, whereas in REPCs, it indirectly induces the release of this hormone. Our findings are also highly relevant to the testing of small molecule PHD inhibitors in phase III clinical trials for patients with renal anemia. KEY MESSAGES: HIF2α and not HIF1α modulates PNMT during epinephrine synthesis in chromaffin cells. The PHD2-HIF2α-EPO axis induces erythrocytosis and hypoglycemia. Reduced systemic glucose facilitates exocytosis of epinephrine from adrenal gland.
Topics: Adrenal Medulla; Animals; Basic Helix-Loop-Helix Transcription Factors; Calcium; Epinephrine; Erythropoietin; Female; Hypoglycemia; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Mice, Transgenic; Phenylethanolamine N-Methyltransferase; Polycythemia; Tumor Cells, Cultured
PubMed: 34480587
DOI: 10.1007/s00109-021-02121-y -
Cancers Feb 2022Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a... (Review)
Review
Pheochromocytomas and abdominal paragangliomas (PPGLs) are rare tumors arising from the adrenal medulla or the sympathetic nervous system. This review presents a practical guidance for clinicians dealing with PPGLs. The incidence of PPGLs has risen. Most cases are detected via imaging and less present with symptoms of catecholamine excess. Most PPGLs secrete catecholamines, with diffuse symptoms. Diagnosis is made by imaging and tests of catecholamines. Localized disease can be cured by surgery. PPGLs are the most heritable of all human tumors, and germline variants are found in approximately 30-50% of cases. Such variants can give information regarding the risk of developing recurrence or metastases as well as the risk of developing other tumors and may identify relatives at risk for disease. All PPGLs harbor malignant potential, and current histological and immunohistochemical algorithms can aid in the identification of indolent vs. aggressive tumors. While most patients with metastatic PPGL have slowly progressive disease, a proportion of patients present with an aggressive course, highlighting the need for more effective therapies in these cases. We conclude that PPGLs are rare but increasing in incidence and management should be guided by a multidisciplinary team.
PubMed: 35205664
DOI: 10.3390/cancers14040917 -
Cellular and Molecular Neurobiology Jan 2021Nicotinic acetylcholine receptors (nAChRs) have gained much attention in the scientific community since they play a significant role in multiple physiological and... (Review)
Review
Nicotinic acetylcholine receptors (nAChRs) have gained much attention in the scientific community since they play a significant role in multiple physiological and pathophysiological processes. Multiple approaches to study the receptors exist, with characterization of the receptors' functionality at a single cellular level using cell culturing being one of them. Derived from an adrenal medulla tumor, PC12 cells express nicotinic receptor subunits and form functional nicotinic receptors. Thus, the cells offer a convenient environment to address questions related to the functionality of the receptors. The review summarizes the findings on nicotinic receptors' expression and functions which were conducted using PC12 cells. Specific focus is given to α3-containing receptors as well as α7 receptor. Critical evaluation of findings is provided alongside insights into what can still be learned about nAChRs, using PC12 cells.
Topics: Animals; Models, Biological; PC12 Cells; Protein Subunits; Rats; Receptors, Nicotinic
PubMed: 32335772
DOI: 10.1007/s10571-020-00846-x -
Cancer Prevention Research... Feb 2020From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief... (Review)
Review
From the time of their introduction, the popularity of e-cigarettes (electronic nicotine-delivery systems) has been rising. This trend may reflect the general belief that e-cigarettes are a less hazardous alternative to combustible cigarettes. However, the potential cancer-related effects of increased activation of the sympathoadrenal system induced by the inhalation of nicotine, the primary component of the e-cigarettes, are completely overlooked. Therefore, the aim of this review is to describe mechanisms that may connect the use of e-cigarettes and an increased risk for cancer development, as well as their stimulatory effect on cancer progression. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms. This issue might be especially important for oncological patients as they may have the misconception that compared with combustible cigarettes, e-cigarettes represent a risk-free alternative.
Topics: Administration, Inhalation; Disease Progression; Electronic Nicotine Delivery Systems; Heating; Humans; Neoplasms; Nicotine; Risk Factors; Smoking; Smoking Cessation; Sympathoadrenal System; Tobacco Products
PubMed: 31619443
DOI: 10.1158/1940-6207.CAPR-19-0346 -
Endocrine-related Cancer Dec 2020Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla or extra-adrenal paraganglia. Around 40% of all cases are... (Review)
Review
Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla or extra-adrenal paraganglia. Around 40% of all cases are caused by a germline mutation in a susceptibility gene, half of which being found in an SDHx gene (SDHA, SDHB, SDHC, SDHD or SDHAF2). They encode the four subunits and assembly factor of succinate dehydrogenase (SDH), a mitochondrial enzyme involved both in the tricarboxylic acid cycle and electron transport chain. SDHx mutations lead to the accumulation of succinate, which acts as an oncometabolite by inhibiting iron(II) and alpha-ketoglutarate-dependent dioxygenases thereby regulating the cell's hypoxic response and epigenetic processes. Moreover, SDHx mutations induce cell metabolic reprogramming and redox imbalance. Major discoveries in PPGL pathophysiology have been made since the initial discovery of SDHD gene mutations in 2000, improving the understanding of their biology and patient management. It indeed provides new opportunities for diagnostic tools and innovative therapeutic targets in order to improve the prognosis of patients affected by these rare tumors, in particular in the context of metastatic diseases associated with SDHB mutations. This review first describes an overview of the pathophysiology and then focuses on clinical implications of the epigenetic and metabolic reprogramming of SDH-deficient PPGL.
Topics: Epigenomics; Female; Humans; Male; Paraganglioma; Succinate Dehydrogenase
PubMed: 33112834
DOI: 10.1530/ERC-20-0346 -
Stem cells, evolutionary aspects and pathology of the adrenal medulla: A new developmental paradigm.Molecular and Cellular Endocrinology Dec 2020The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the... (Review)
Review
The mammalian adrenal gland is composed of two main components; the catecholaminergic neural crest-derived medulla, found in the center of the gland, and the mesoderm-derived cortex producing steroidogenic hormones. The medulla is composed of neuroendocrine chromaffin cells with oxygen-sensing properties and is dependent on tissue interactions with the overlying cortex, both during development and in adulthood. Other relevant organs include the Zuckerkandl organ containing extra-adrenal chromaffin cells, and carotid oxygen-sensing bodies containing glomus cells. Chromaffin and glomus cells reveal a number of important similarities and are derived from the multipotent nerve-associated descendants of the neural crest, or Schwann cell precursors. Abnormalities in complex developmental processes during differentiation of nerve-associated and other progenitors into chromaffin and oxygen-sensing populations may result in different subtypes of paraganglioma, neuroblastoma and pheochromocytoma. Here, we summarize recent findings explaining the development of chromaffin and oxygen-sensing cells, as well as the potential mechanisms driving neuroendocrine tumor initiation.
Topics: Adrenal Gland Diseases; Adrenal Medulla; Animals; Biological Evolution; Cell Differentiation; Humans; Neural Crest; Stem Cells
PubMed: 32818585
DOI: 10.1016/j.mce.2020.110998 -
Cureus Nov 2022Pheochromocytomas are rare tumors located in the adrenal medulla, that derives from the chromaffin cells and produce catecholamines. They are an uncommon cause of...
Pheochromocytomas are rare tumors located in the adrenal medulla, that derives from the chromaffin cells and produce catecholamines. They are an uncommon cause of hypertension, and only 50% of the patients present symptoms compatible with this pathology. Here we describe the case of a 70-year-old woman with a history of anxiety, hypertension and palpitation, who had an unspecified nodule in the right adrenal gland. Laboratory studies revealed an elevated urinary metanephrines secretion. A diagnosis of pheochromocytoma was made and an adrenalectomy was performed. Our aim is to highlight the diagnosis of this rare tumor and how its early management can prevent morbidity and mortality.
PubMed: 36523722
DOI: 10.7759/cureus.31409 -
Surgical Oncology Clinics of North... Apr 2021Pediatric adrenal tumors are uncommon entities that are frequently occult and identified incidentally or by recognizing symptoms related to hormone overproduction. They... (Review)
Review
Pediatric adrenal tumors are uncommon entities that are frequently occult and identified incidentally or by recognizing symptoms related to hormone overproduction. They often have a genetic underpinning, arise from the medulla or cortex, can be malignant or benign, and require precise diagnostic algorithms. However, pseudotumors must also be a diagnostic consideration. Therapeutic interventions and plans are tumor dependent, but surgery is a cornerstone of treatment. Ongoing surveillance after treatment, regardless of malignant determination, is of utmost importance as well.
Topics: Adrenal Gland Neoplasms; Child; Humans
PubMed: 33706900
DOI: 10.1016/j.soc.2020.11.012