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EBioMedicine Jan 2024The long-standing view of senescent cells as passive and dysfunctional biological remnants has recently shifted into a new paradigm where they are main players in the... (Review)
Review
The long-standing view of senescent cells as passive and dysfunctional biological remnants has recently shifted into a new paradigm where they are main players in the development of many diseases, including cancer. The senescence programme represents a first line of defence that prevents tumour cell growth but also leads to the secretion of multiple pro-inflammatory and pro-tumourigenic factors that fuel tumour initiation, growth, and progression. Here, we review the main molecular features and biological functions of senescent cells in cancer, including the outcomes of inducing or targeting senescence. We discuss evidence on the role of cellular senescence in pituitary tumours, with an emphasis on adamantinomatous craniopharyngioma (ACP) and pituitary adenomas. Although senescence has been proposed to be a tumour-preventing mechanism in pituitary adenomas, research in ACP has shown that senescent cells are tumour-promoting in both murine models and human tumours. Future studies characterizing the impact of targeting senescent cells may result in novel therapies against pituitary tumours.
Topics: Humans; Mice; Child; Animals; Pituitary Neoplasms; Pituitary Gland; Craniopharyngioma; Carcinogenesis; Cell Transformation, Neoplastic; Cellular Senescence
PubMed: 38043401
DOI: 10.1016/j.ebiom.2023.104905 -
Frontiers in Endocrinology 2024Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of... (Review)
Review
Prolactinomas (PRLomas) constitute approximately half of all pituitary adenomas and approximately one-fifth of them are diagnosed in males. The clinical presentation of PRLomas results from direct prolactin (PRL) action, duration and severity of hyperprolactinemia, and tumor mass effect. Male PRLomas, compared to females, tend to be larger and more invasive, are associated with higher PRL concentration at diagnosis, present higher proliferative potential, are more frequently resistant to standard pharmacotherapy, and thus may require multimodal approach, including surgical resection, radiotherapy, and alternative medical agents. Therefore, the management of PRLomas in men is challenging in many cases. Additionally, hyperprolactinemia is associated with a significant negative impact on men's health, including sexual function and fertility potential, bone health, cardiovascular and metabolic complications, leading to decreased quality of life. In this review, we highlight the differences in pathogenesis, clinical presentation and treatment of PRLomas concerning the male sex.
Topics: Female; Male; Humans; Prolactinoma; Hyperprolactinemia; Quality of Life; Pituitary Neoplasms; Adenoma
PubMed: 38370355
DOI: 10.3389/fendo.2024.1338345 -
Endocrine Reviews Sep 2023The vital physiological role of the pituitary gland, alongside its proximity to critical neurovascular structures, means that pituitary adenomas can cause significant...
The vital physiological role of the pituitary gland, alongside its proximity to critical neurovascular structures, means that pituitary adenomas can cause significant morbidity or mortality. While enormous advancements have been made in the surgical care of pituitary adenomas, numerous challenges remain, such as treatment failure and recurrence. To meet these clinical challenges, there has been an enormous expansion of novel medical technologies (eg, endoscopy, advanced imaging, artificial intelligence). These innovations have the potential to benefit each step of the patient's journey, and ultimately, drive improved outcomes. Earlier and more accurate diagnosis addresses this in part. Analysis of novel patient data sets, such as automated facial analysis or natural language processing of medical records holds potential in achieving an earlier diagnosis. After diagnosis, treatment decision-making and planning will benefit from radiomics and multimodal machine learning models. Surgical safety and effectiveness will be transformed by smart simulation methods for trainees. Next-generation imaging techniques and augmented reality will enhance surgical planning and intraoperative navigation. Similarly, surgical abilities will be augmented by the future operative armamentarium, including advanced optical devices, smart instruments, and surgical robotics. Intraoperative support to surgical team members will benefit from a data science approach, utilizing machine learning analysis of operative videos to improve patient safety and orientate team members to a common workflow. Postoperatively, neural networks leveraging multimodal datasets will allow early detection of individuals at risk of complications and assist in the prediction of treatment failure, thus supporting patient-specific discharge and monitoring protocols. While these advancements in pituitary surgery hold promise to enhance the quality of care, clinicians must be the gatekeepers of the translation of such technologies, ensuring systematic assessment of risk and benefit prior to clinical implementation. In doing so, the synergy between these innovations can be leveraged to drive improved outcomes for patients of the future.
Topics: Humans; Pituitary Neoplasms; Artificial Intelligence; Adenoma; Endoscopy
PubMed: 37207359
DOI: 10.1210/endrev/bnad014 -
Neuro-oncology Jul 2023A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain...
BACKGROUND
A methylation-based classification of ependymoma has recently found broad application. However, the diagnostic advantage and implications for treatment decisions remain unclear. Here, we retrospectively evaluate the impact of surgery and radiotherapy on outcome after molecular reclassification of adult intracranial ependymomas.
METHODS
Tumors diagnosed as intracranial ependymomas from 170 adult patients collected from 8 diagnostic institutions were subjected to DNA methylation profiling. Molecular classes, patient characteristics, and treatment were correlated with progression-free survival (PFS).
RESULTS
The classifier indicated an ependymal tumor in 73.5%, a different tumor entity in 10.6%, and non-classifiable tumors in 15.9% of cases, respectively. The most prevalent molecular classes were posterior fossa ependymoma group B (EPN-PFB, 32.9%), posterior fossa subependymoma (PF-SE, 25.9%), and supratentorial ZFTA fusion-positive ependymoma (EPN-ZFTA, 11.2%). With a median follow-up of 60.0 months, the 5- and 10-year-PFS rates were 64.5% and 41.8% for EPN-PFB, 67.4% and 45.2% for PF-SE, and 60.3% and 60.3% for EPN-ZFTA. In EPN-PFB, but not in other molecular classes, gross total resection (GTR) (P = .009) and postoperative radiotherapy (P = .007) were significantly associated with improved PFS in multivariable analysis. Histological tumor grading (WHO 2 vs. 3) was not a predictor of the prognosis within molecularly defined ependymoma classes.
CONCLUSIONS
DNA methylation profiling improves diagnostic accuracy and risk stratification in adult intracranial ependymoma. The molecular class of PF-SE is unexpectedly prevalent among adult tumors with ependymoma histology and relapsed as frequently as EPN-PFB, despite the supposed benign nature. GTR and radiotherapy may represent key factors in determining the outcome of EPN-PFB patients.
Topics: Adult; Humans; Retrospective Studies; DNA Methylation; Prognosis; Brain Neoplasms; Ependymoma
PubMed: 36734226
DOI: 10.1093/neuonc/noad030 -
Frontiers in Endocrinology 2023Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Somatotropinomas are the main cause of acromegaly. Surgery is the primary and most efficient method of treatment. The study aimed to compare the radicality of small-sized and medium (<30 mm) somatotropinoma removal and the incidence of postoperative complications in patients with acromegaly when using microscopic and endoscopic techniques.
METHODS
In this randomized controlled trial, a total of 83 patients with acromegaly underwent transspheroidal endoscopy or microscopic surgery. Somatotropinoma was the cause of acromegaly in all cases. Patients were randomly divided into two comparison groups depending on the applied surgical technique. Group 1 (n = 40) consisted of patients who underwent adenomectomy with transnasal transsphenoidal access by a microscope. Group 2 (n = 43) included patients who underwent the same surgical procedure with an endoscope. The following indicators were assessed: radicality of tumor removal, treatment effectiveness, postoperative complications, and remission rate.
RESULTS
The study has shown that removal of somatotropinoma in patients with acromegaly using endoscopic technique increases the radicality of tumor removal in comparison with microscopic technique. Total removal of somatotropinoma was successful in 88.4% of cases when using the endoscopic technique. Secondly, the segmentation of patients according to their tumor characteristics poses challenges, primarily owing to the rarity of acromegaly as a disease. The difference between groups was not statistically significant (p=1.02). There were no statistically significant differences in basal GH level and IGF-1 level between groups (p=0.546 and p=0.784, respectively).
DISCUSSION
Endonasal transsphenoidal endoscopic adenomectomy is proven efficacy, a less traumatic degree, and higher somatotropinoma removal radicality. Both surgical methods lead to disease remission.
Topics: Humans; Acromegaly; Endoscopy; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Postoperative Complications; Pituitary Neoplasms
PubMed: 37766690
DOI: 10.3389/fendo.2023.1128345 -
Frontiers in Endocrinology 2023The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central... (Review)
Review
The role of the gut microbiome has been widely discussed in numerous works of literature. The biggest concern is the association of the gut microbiome with the central nervous system through the microbiome-brain-gut axis in the past ten years. As more and more research has been done on the relationship between the disease of the central nervous system and gut microbes. This fact is being revealed that gut microbes seem to play an important role from the onset and progression of the disease to clinical symptoms, and new treatments. As a special tumor of the central nervous system, pituitary neuroendocrine tumors (PitNETs)are closely related to metabolism, endocrinology, and immunity. These factors are the vectors through which intestinal microbes interact with the central nervous system. However, little is known about the effects of gut microbes on the PitNET. In this review, the relationship of gut microbiota in PitNETs is introduced, the potential effects of the gut-brain axis in this relationship are analyzed, and future research directions are presented.
Topics: Humans; Gastrointestinal Microbiome; Brain; Central Nervous System; Pituitary Neoplasms; Neuroendocrine Tumors
PubMed: 38027221
DOI: 10.3389/fendo.2023.1255911 -
Endocrine Nov 2023To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and...
PURPOSE
To evaluate the incidence of malignancies in acromegaly and to identify risk factors for newly-diagnostic cancers, especially the excessive growth hormone (GH) and insulin-like growth factor-1 (IGF-1).
METHODS
A retrospective cohort including 1738 consecutive hospitalized patients with acromegaly in a single referral center between 2012 and 2020 (mean follow-up 4.3 years). A gender- and age-matched case-control study (280 patients from the cohort) was performed for risk factor analysis.
RESULTS
One hundred thirteen malignancies (67 diagnosed after acromegaly) were observed. The overall newly-diagnostic cancer risk of acromegaly was higher than the general population (standardized incidence ratio (SIR) 2.81; 95% CI 2.18-3.57). The risk of thyroid cancer (n = 33, SIR 21.42; 95% CI 13.74-30.08) and colorectal cancer (n = 8, SIR 3.17; 95% CI 1.37-6.25) was elevated. In the overall cohort, IGF-1 (ULN: 1.27 vs. 0.94, p = 0.057), GH (1.30 vs. 1.00 ng/ml, p = 0.12), and disease-controlled rate (34.9% vs. 45.9%, p = 0.203) at the last visit did not reach significance between patients with and without post-diagnostic cancer. In the case-control study, GH (1.80 vs. 0.90 ng/ml, p = 0.018) and IGF-1 (ULN: 1.27 vs. 0.91, p = 0.003) at the last visit were higher in patients with post-diagnostic cancers, with a lower disease-controlled rate. Elder age was a risk factor for cancer. Other metabolic comorbidities and the size of pituitary tumors were similar.
CONCLUSION
The risk of malignancies, especially thyroid cancer, was increased in patients with acromegaly in our center. More cancer screening should be considered when managing acromegaly, especially in patients with higher posttreatment GH and IGF-1.
Topics: Humans; Aged; Acromegaly; Retrospective Studies; Insulin-Like Growth Factor I; Case-Control Studies; Incidence; East Asian People; Pituitary Neoplasms; Thyroid Neoplasms; Risk Factors; Human Growth Hormone
PubMed: 37442901
DOI: 10.1007/s12020-023-03447-y -
Brain Pathology (Zurich, Switzerland) Sep 2023Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile...
A comprehensive analysis of infantile central nervous system tumors to improve distinctive criteria for infant-type hemispheric glioma versus desmoplastic infantile ganglioglioma/astrocytoma.
Recent epigenomic analyses have revealed the existence of a new DNA methylation class (MC) of infant-type hemispheric glioma (IHG). Like desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA), these tumors mainly affect infants and are supratentorial. While DIG/DIA is characterized by BRAF or RAF1 alterations, IHG has been shown to have receptor tyrosine kinase (RTK) gene fusions (ALK, ROS1, NTRK1/2/3, and MET). However, in this rapidly evolving field, a more comprehensive analysis of infantile glial/glioneuronal tumors including clinical, radiological, histopathological, and molecular data is needed. Here, we retrospectively investigated data from 30 infantile glial/glioneuronal tumors, consecutively compiled from our center. They were analyzed by two experienced pediatric neuroradiologists in consensus, without former knowledge of the molecular data. We also performed a comprehensive clinical, and histopathological examination (including molecular evaluation by next-generation sequencing, RNA sequencing, and fluorescence in situ hybridization [FISH] analyses), as well as DNA methylation profiling for the samples having sufficient material available. The integrative histopathological, genetic, and epigenetic analyses, including t-distributed stochastic neighbor embedding (t-SNE) analyses segregated tumors into 10 DIG/DIA (33.3%), six IHG (20.0%), three gangliogliomas (10.0%), two pleomorphic xanthoastrocytomas (6.7%), two pilocytic astrocytomas (6.7%), two supratentorial ependymomas, ZFTA fusion-positive (6.7%), two supratentorial ependymomas, YAP1 fusion-positive (6.7%), two embryonal tumors with PLAGL2-family amplification (6.7%), and one diffuse low-grade glioma, MAPK-pathway altered. This study highlights the significant differential features, in terms of histopathology (leptomeningeal infiltration, intense desmoplasia and ganglion cells in DIG/DIA and necrosis, microvascular proliferation, and siderophages in IHG), and radiology between DIG/DIA and IHG. Moreover, these results are consistent with the literature data concerning the molecular dichotomy (BRAF/RAF1 alterations vs. RTK genes' fusions) between DIG/DIA and IHG. This study characterized histopathologically and radiologically two additional cases of the novel embryonal tumor characterized by PLAGL2 gene amplification.
Topics: Humans; Ganglioglioma; Brain Neoplasms; Proto-Oncogene Proteins B-raf; Retrospective Studies; In Situ Hybridization, Fluorescence; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Astrocytoma; Central Nervous System Neoplasms; Neoplasms, Neuroepithelial; Ependymoma; DNA-Binding Proteins; Transcription Factors; RNA-Binding Proteins
PubMed: 37349135
DOI: 10.1111/bpa.13182 -
The Pan African Medical Journal 2023Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1)....
Acromegaly is defined as an acquired dysmorphytic syndrome due to excessive secretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). This is a retrospective study of patients who were hospitalized in the Endocrinology Department of the Mohammed V Military Academic Hospital in Rabat over a period of 14 years (2008 to 2022), reporting on their clinical, paraclinical and evolutionary profiles and comparing the results with the data in the literature. Nineteen patients were included in our study. The mean age was 42.7 ± 11.6 years, with a male predominance. The clinical manifestations were dominated by a dysmorphic syndrome present in 97.4% of cases, followed by complications related to acromegaly in 88.9% of cases. The diagnosis was made when GH and IGF-1 values were elevated in 88.9% and 93.8% of cases, respectively; with a mean GH value of 25.1 μg/L. Magnetic resonance imaging (MRI) was used to diagnose the location of pituitary adenoma in all cases, 78.9% of which were macroadenomas and 21.1% microadenomas. The majority of patients (78.9%) had recourse to transsphenoidal surgery. Medical treatment was carried out in 89.5% of cases. Postoperative radiotherapy was performed in 33% of cases. Disease control was achieved in 30.1% of cases. This study shows the complex management of acromegaly. Disease control is a necessary condition in order to avoid complications, but is often difficult to obtain.
Topics: Humans; Male; Adult; Middle Aged; Female; Acromegaly; Insulin-Like Growth Factor I; Retrospective Studies; Treatment Outcome; Human Growth Hormone; Pituitary Neoplasms
PubMed: 38465009
DOI: 10.11604/pamj.2023.46.116.41952 -
CNS Neuroscience & Therapeutics Oct 2023Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign... (Review)
Review
Pituitary adenomas (PAs), or pituitary neuroendocrine tumors (PitNETs), are commonly found in the anterior pituitary gland. Although the majority of PitNETs are benign and stable, several tumors have malignant characteristics. The tumor microenvironment (TME) plays an important role in the process of tumorigenesis and is composed of several types of cells. Various cells in the TME are significantly affected by oxidative stress. It has been reported that immunotherapeutic strategies have good effects in several cancers. However, the clinical potential of immunotherapies in PitNETs has not yet been fully discussed. Oxidative stress can regulate PitNET cells and immune cells in the TME, thus affecting the immune status of the TME of PitNETs. Therefore, modulation of oxidative stress-regulated immune cells using a combination of several agents and the immune system to suppress PitNETs is a promising therapeutic direction. In this review, we systematically analyzed the oxidative stress process within PitNET cells and various immune cells to elucidate the potential value of immunotherapy.
Topics: Humans; Pituitary Neoplasms; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 37341156
DOI: 10.1111/cns.14315