@article{MTMT:34753298, title = {The Immune Landscape of Pheochromocytoma and Paraganglioma: Current Advances and Perspectives}, url = {https://m2.mtmt.hu/api/publication/34753298}, author = {Uher, Ondrej and Vanova, Katerina Hadrava and Taieb, David and Calsina, Bruna and Robledo, Mercedes and Clifton-Bligh, Roderick and Pacak, Karel}, doi = {10.1210/endrev/bnae005}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34753298}, issn = {0163-769X}, abstract = {Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells from adrenal medullary chromaffin tissues and extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal treatment options for advanced and metastatic cases have been limited. Hence, understanding the role of the immune system in PPGL tumorigenesis can provide essential knowledge for the development of better therapeutic and tumor management strategies, especially for those with advanced and metastatic PPGLs. The first part of this review outlines the fundamental principles of the immune system and tumor microenvironment, and their role in cancer immunoediting, particularly emphasizing PPGLs. We focus on how the unique pathophysiology of PPGLs, such as their high molecular, biochemical, and imaging heterogeneity and production of several oncometabolites, creates a tumor-specific microenvironment and immunologically "cold" tumors. Thereafter, we discuss recently published studies related to the reclustering of PPGLs based on their immune signature. The second part of this review discusses future perspectives in PPGL management, including immunodiagnostic and promising immunotherapeutic approaches for converting "cold" tumors into immunologically active or "hot" tumors known for their better immunotherapy response and patient outcomes. Special emphasis is placed on potent immune-related imaging strategies and immune signatures that could be used for the reclassification, prognostication, and management of these tumors to improve patient care and prognosis. Furthermore, we introduce currently available immunotherapies and their possible combinations with other available therapies as an emerging treatment for PPGLs that targets hostile tumor environments. Graphical Abstract}, keywords = {T-CELLS; PERSPECTIVES; cancer immunotherapy; CELL LUNG-CANCER; pheochromocytoma; tumor-associated macrophages; Paraganglioma; Neuroendocrine tumors; phase I/II; somatostatin receptors; neuroendocrine neoplasms; ARTIFICIAL-INTELLIGENCE; INTRATUMORAL IMMUNOTHERAPY; SPORADIC PHEOCHROMOCYTOMAS}, year = {2024}, eissn = {1945-7189}, orcid-numbers = {Uher, Ondrej/0000-0003-3978-9822; Calsina, Bruna/0000-0002-6922-9415; Robledo, Mercedes/0000-0001-6256-5902; Clifton-Bligh, Roderick/0000-0002-1545-0368} } @article{MTMT:34666713, title = {Genetic and Epigenetic Landscape for Drug Development in Polycystic Ovary Syndrome}, url = {https://m2.mtmt.hu/api/publication/34666713}, author = {Chen, Yi and Wang, Guiquan and Chen, Jingqiao and Wang, Congying and Dong, Xi and Chang, Hsun-Ming and Yuan, Shuai and Zhao, Yue and Mu, Liangshan}, doi = {10.1210/endrev/bnae002}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34666713}, issn = {0163-769X}, keywords = {GENETICS; pharmacotherapy; Gene Therapy; Polycystic Ovary Syndrome; epigenetics}, year = {2024}, eissn = {1945-7189}, orcid-numbers = {Yuan, Shuai/0000-0001-5055-5627} } @article{MTMT:34659501, title = {Imaging of Pheochromocytomas and Paragangliomas}, url = {https://m2.mtmt.hu/api/publication/34659501}, author = {Timmers, Henri J. L. M. and Taieb, David and Pacak, Karel and Lenders, Jacques W. M.}, doi = {10.1210/endrev/bnae001}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34659501}, issn = {0163-769X}, keywords = {PET; CT; SPECT; MRI; pheochromocytoma; Paraganglioma}, year = {2024}, eissn = {1945-7189} } @article{MTMT:34608091, title = {The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa}, url = {https://m2.mtmt.hu/api/publication/34608091}, author = {Rosenstock, Julio and Juneja, Rattan and Beals, John M. and Moyers, Julie S. and Ilag, Liza and McCrimmon, Rory J.}, doi = {10.1210/endrev/bnad037}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34608091}, issn = {0163-769X}, abstract = {Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia. Advances over the last 2 decades have resulted in long-acting, soluble basal insulin analogues with prolonged and less variable pharmacokinetic exposure, improving their efficacy and safety, notably by reducing nocturnal hypoglycemia. However, adherence and persistence with once-daily basal insulin treatment remains low for many reasons including hypoglycemia concerns and treatment burden. A soluble basal insulin with a longer and flatter exposure profile could reduce pharmacodynamic variability, potentially reducing hypoglycemia, have similar efficacy to once-daily basal insulins, simplify dosing regimens, and improve treatment adherence. Insulin icodec (Novo Nordisk) and insulin efsitora alfa (basal insulin Fc [BIF], Eli Lilly and Company) are 2 such insulins designed for once-weekly administration, which have the potential to provide a further advance in basal insulin replacement. Icodec and efsitora phase 2 clinical trials, as well as data from the phase 3 icodec program indicate that once-weekly insulins provide comparable glycemic control to once-daily analogues, with a similar risk of hypoglycemia. This manuscript details the technology used in the development of once-weekly basal insulins. It highlights the clinical rationale and potential benefits of these weekly insulins while also discussing the limitations and challenges these molecules could pose in clinical practice.Graphical Abstract}, keywords = {hypoglycemia; Basal insulin; insulin icodec; Once-weekly insulin; insulin efsitora; peak-to-trough ratio}, year = {2024}, eissn = {1945-7189} } @article{MTMT:34805584, title = {Biomarkers to Guide Medical Therapy in Primary Aldosteronism}, url = {https://m2.mtmt.hu/api/publication/34805584}, author = {Hundemer, G.L. and Leung, A.A. and Kline, G.A. and Brown, J.M. and Turcu, A.F. and Vaidya, A.}, doi = {10.1210/endrev/bnad024}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, volume = {45}, unique-id = {34805584}, issn = {0163-769X}, abstract = {Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed. © 2023 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.}, keywords = {Humans; PHENOTYPE; Adrenalectomy; RENIN; RENIN; RENIN; RENIN; PATHOPHYSIOLOGY; POTASSIUM; review; human; Biomarkers; Biomarkers; HYPERTENSION; HYPERTENSION; antiandrogen; biological marker; biological marker; Comorbidity; UNCERTAINTY; Consensus; cardiovascular disease; kidney disease; chronic kidney failure; heart function; Hypokalemia; spironolactone; hyperaldosteronism; hyperaldosteronism; hyperaldosteronism; aldosterone; aldosterone; aldosterone; aldosterone; treatment indication; practice guideline; risk reduction; sodium chloride; Amiloride; target organ; blood pressure measurement; antihypertensive agent; Clinical outcome; blood pressure regulation; pharmaceutical care; gestagen; hyperkalemia; hormone synthesis; potassium blood level; Atrial Fibrillation; sodium restriction; Mineralocorticoid Receptor Antagonists; Mineralocorticoid Receptor Antagonists; oxygenase inhibitor; primary hyperaldosteronism; Primary aldosteronism; finerenone; aldosterone synthase; mineralocorticoid antagonist; Prescribing practice; Esaxerenone; triamterene; epithelial sodium channel blocking agent; kaliuresis; ocedurenone}, year = {2024}, eissn = {1945-7189}, pages = {69-94} } @article{MTMT:34233218, title = {The Emerging Therapeutic Potential of Kisspeptin and Neurokinin B}, url = {https://m2.mtmt.hu/api/publication/34233218}, author = {Patel, Bijal and Koysombat, Kanyada and Mills, Edouard G. and Tsoutsouki, Jovanna and Comninos, Alexander N. and Abbara, Ali and Dhillo, Waljit S.}, doi = {10.1210/endrev/bnad023}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, volume = {45}, unique-id = {34233218}, issn = {0163-769X}, abstract = {Kisspeptin (KP) and neurokinin B (NKB) are neuropeptides that govern the reproductive endocrine axis through regulating hypothalamic gonadotropin-releasing hormone (GnRH) neuronal activity and pulsatile GnRH secretion. Their critical role in reproductive health was first identified after inactivating variants in genes encoding for KP or NKB signaling were shown to result in congenital hypogonadotropic hypogonadism and a failure of pubertal development. Over the past 2 decades since their discovery, a wealth of evidence from both basic and translational research has laid the foundation for potential therapeutic applications. Beyond KP's function in the hypothalamus, it is also expressed in the placenta, liver, pancreas, adipose tissue, bone, and limbic regions, giving rise to several avenues of research for use in the diagnosis and treatment of pregnancy, metabolic, liver, bone, and behavioral disorders. The role played by NKB in stimulating the hypothalamic thermoregulatory center to mediate menopausal hot flashes has led to the development of medications that antagonize its action as a novel nonsteroidal therapeutic agent for this indication. Furthermore, the ability of NKB antagonism to partially suppress (but not abolish) the reproductive endocrine axis has supported its potential use for the treatment of various reproductive disorders including polycystic ovary syndrome, uterine fibroids, and endometriosis. This review will provide a comprehensive up-to-date overview of the preclinical and clinical data that have paved the way for the development of diagnostic and therapeutic applications of KP and NKB.}, keywords = {BEHAVIOR; metabolism; reproduction; Bone; kisspeptin; neurokinin B}, year = {2024}, eissn = {1945-7189}, pages = {30-68}, orcid-numbers = {Abbara, Ali/0000-0003-2795-5256} } @article{MTMT:34577856, title = {Appetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity}, url = {https://m2.mtmt.hu/api/publication/34577856}, author = {Gan, Hoong-Wei and Cerbone, Manuela and Dattani, Mehul Tulsidas}, doi = {10.1210/endrev/bnad033}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34577856}, issn = {0163-769X}, abstract = {Since hypothalamic obesity (HyOb) was first described over 120 years ago by Joseph Babinski and Alfred Frohlich, advances in molecular genetic laboratory techniques have allowed us to elucidate various components of the intricate neurocircuitry governing appetite and weight regulation connecting the hypothalamus, pituitary gland, brainstem, adipose tissue, pancreas, and gastrointestinal tract. On a background of an increasing prevalence of population-level common obesity, the number of survivors of congenital (eg, septo-optic dysplasia, Prader-Willi syndrome) and acquired (eg, central nervous system tumors) hypothalamic disorders is increasing, thanks to earlier diagnosis and management as well as better oncological therapies. Although to date the discovery of several appetite-regulating peptides has led to the development of a range of targeted molecular therapies for monogenic obesity syndromes, outside of these disorders these discoveries have not translated into the development of efficacious treatments for other forms of HyOb. This review aims to summarize our current understanding of the neuroendocrine physiology of appetite and weight regulation, and explore our current understanding of the pathophysiology of HyOb.Graphical Abstract}, keywords = {OBESITY; Appetite; hypothalamus; anorexigen; orexigen}, year = {2023}, eissn = {1945-7189}, orcid-numbers = {Gan, Hoong-Wei/0000-0001-6198-0397; Cerbone, Manuela/0000-0003-3472-0746} } @article{MTMT:34471469, title = {Diabetes Mellitus, Energy Metabolism, and COVID-19}, url = {https://m2.mtmt.hu/api/publication/34471469}, author = {Conte, Caterina and Cipponeri, Elisa and Roden, Michael}, doi = {10.1210/endrev/bnad032}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, volume = {In press}, unique-id = {34471469}, issn = {0163-769X}, abstract = {Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic. Graphical Abstract}, keywords = {LIVER; PANCREAS; skeletal muscle; MITOCHONDRIAL-FUNCTION; BODY-MASS INDEX; Adipose Tissue; INDUCED INSULIN-RESISTANCE; BLOOD-GLUCOSE CONTROL; NLRP3 INFLAMMASOME; beta-cell function; SARS-CoV-2; ACUTE RESPIRATORY SYNDROME; VISCERAL ADIPOSE-TISSUE; SARS-CoV-2 infection}, year = {2023}, eissn = {1945-7189}, pages = {In press}, orcid-numbers = {Conte, Caterina/0000-0001-7066-5292} } @article{MTMT:34366818, title = {The Pregnancy-Associated Plasma Protein-A (PAPP-A) Story}, url = {https://m2.mtmt.hu/api/publication/34366818}, author = {Conover, Cheryl A. and Oxvig, Claus}, doi = {10.1210/endrev/bnad017}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34366818}, issn = {0163-769X}, abstract = {Pregnancy-associated plasma protein-A (PAPP-A) was first identified in the early 1970s as a placental protein of unknown function, present at high concentrations in the circulation of pregnant women. In the mid-to-late 1990s, PAPP-A was discovered to be a metzincin metalloproteinase, expressed by many nonplacental cells, that regulates local insulin-like growth factor (IGF) activity through cleavage of high-affinity IGF binding proteins (IGFBPs), in particular IGFBP-4. With PAPP-A as a cell surface-associated enzyme, the reduced affinity of the cleavage fragments results in increased IGF available to bind and activate IGF receptors in the pericellular environment. This proteolytic regulation of IGF activity is important, since the IGFs promote proliferation, differentiation, migration, and survival in various normal and cancer cells. Thus, there has been a steady growth in investigation of PAPP-A structure and function outside of pregnancy. This review provides historical perspective on the discovery of PAPP-A and its structure and cellular function, highlights key studies of the first 50 years in PAPP-A research, and introduces new findings from recent years.}, keywords = {CANCER; Insulin-like growth factor; organ systems; insulin-like growth factor binding protein-4; Pregnancy-associated plasma protein-A (PAPP-A)}, year = {2023}, eissn = {1945-7189}, orcid-numbers = {Oxvig, Claus/0000-0002-4715-9719} } @article{MTMT:34359595, title = {Update on Adipose Tissue and Cancer}, url = {https://m2.mtmt.hu/api/publication/34359595}, author = {Brown, Kristy A. and Scherer, Philipp E.}, doi = {10.1210/endrev/bnad015}, journal-iso = {ENDOCR REV}, journal = {ENDOCRINE REVIEWS}, unique-id = {34359595}, issn = {0163-769X}, abstract = {Adipose tissue is the largest endocrine organ and an accepted contributor to overall energy homeostasis. There is strong evidence linking increased adiposity to the development of 13 types of cancer. With increased adiposity comes metabolic dysfunction and insulin resistance, and increased systemic insulin and glucose support the growth of many cancers, including those of the colon and endometrium. There is also an important direct crosstalk between adipose tissue and various organs. For instance, the healthy development and function of the mammary gland, as well as the development, growth, and progression of breast cancer, are heavily impacted by the breast adipose tissue in which breast epithelial cells are embedded. Cells of the adipose tissue are responsive to external stimuli, including overfeeding, leading to remodeling and important changes in the secretion of factors known to drive the development and growth of cancers. Loss of factors like adiponectin and increased production of leptin, endotrophin, steroid hormones, and inflammatory mediators have been determined to be important mediators of the obesity-cancer link. Obesity is also associated with a structural remodeling of the adipose tissue, including increased localized fibrosis and disrupted angiogenesis that contribute to the development and progression of cancers. Furthermore, tumor cells feed off the adipose tissue, where increased lipolysis within adipocytes leads to the release of fatty acids and stromal cell aerobic glycolysis leading to the increased production of lactate. Both have been hypothesized to support the higher energetic demands of cancer cells. Here, we aim to provide an update on the state of the literature revolving around the role of the adipose tissue in cancer initiation and progression.}, keywords = {CANCER; OBESITY; Adipokines; Adipose Tissue}, year = {2023}, eissn = {1945-7189} }