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PloS One 2024Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in...
Host-defence caerin 1.1 and 1.9 peptides suppress glioblastoma U87 and U118 cell proliferation through the modulation of mitochondrial respiration and induce the downregulation of CHI3L1.
Glioblastoma, the most aggressive form of brain cancer, poses a significant global health challenge with a considerable mortality rate. With the predicted increase in glioblastoma incidence, there is an urgent need for more effective treatment strategies. In this study, we explore the potential of caerin 1.1 and 1.9, host defence peptides derived from an Australian tree frog, in inhibiting glioblastoma U87 and U118 cell growth. Our findings demonstrate the inhibitory impact of caerin 1.1 and 1.9 on cell growth through CCK8 assays. Additionally, these peptides effectively curtail the migration of glioblastoma cells in a cell scratch assay, exhibiting varying inhibitory effects among different cell lines. Notably, the peptides hinder the G0/S phase replication in both U87 and U118 cells, pointing to their impact on the cell cycle. Furthermore, caerin 1.1 and 1.9 show the ability to enter the cytoplasm of glioblastoma cells, influencing the morphology of mitochondria. Proteomics experiments reveal intriguing insights, with a decrease in CHI3L1 expression and an increase in PZP and JUNB expression after peptide treatment. These proteins play roles in cell energy metabolism and inflammatory response, suggesting a multifaceted impact on glioblastoma cells. In conclusion, our study underscores the substantial anticancer potential of caerin 1.1 and 1.9 against glioblastoma cells. These findings propose the peptides as promising candidates for further exploration in the realm of glioblastoma management, offering new avenues for developing effective treatment strategies.
Topics: Glioblastoma; Humans; Cell Proliferation; Mitochondria; Cell Line, Tumor; Down-Regulation; Cell Respiration; Animals; Brain Neoplasms; Antimicrobial Cationic Peptides; Cell Movement
PubMed: 38848430
DOI: 10.1371/journal.pone.0304149 -
PloS One 2024Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting...
Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting endocrine abnormalities, which seriously affect the quality of life of patients. Patients with craniopharyngiomas are at higher cardiometabolic risk, defined as conditions favoring the development of type 2 diabetes and cardiovascular disease. However, the underlying common pathogenic mechanisms of craniopharyngiomas and type 2 diabetes are not clear. Especially due to the difficulty of conducting in vitro or in vivo experiments on craniopharyngioma, we thought the common pathway analysis between craniopharyngioma and type 2 diabetes based on bioinformatics is a powerful and feasible method. In the present study, using public datasets (GSE94349, GSE68015, GSE38642 and GSE41762) obtained from the GEO database, the gene expression associated with adamantinomatous craniopharyngioma, a subtype of craniopharyngioma, and type 2 diabetes were analyzed using a bioinformatic approach. We found 11 hub genes using a protein-protein interaction network analysis. Of these, seven (DKK1, MMP12, KRT14, PLAU, WNT5B, IKBKB, and FGF19) were also identified by least absolute shrinkage and selection operator analysis. Finally, single-gene validation and receptor operating characteristic analysis revealed that four of these genes (MMP12, PLAU, KRT14, and DKK1) may be involved in the common pathogenetic mechanism of adamantinomatous craniopharyngioma and type 2 diabetes. In addition, we have characterized the differences in immune cell infiltration that characterize these two diseases, providing a reference for further research.
Topics: Humans; Craniopharyngioma; Diabetes Mellitus, Type 2; Computational Biology; Pituitary Neoplasms; Protein Interaction Maps; Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Gene Expression Profiling; Biomarkers
PubMed: 38848397
DOI: 10.1371/journal.pone.0304404 -
Free Neuropathology Jan 2024: Cells with stem cell features have been described in pituitary neuroendocrine tumours (PitNETs). Transcription factors SOX2 and SOX9 are stem cell-associated markers...
: Cells with stem cell features have been described in pituitary neuroendocrine tumours (PitNETs). Transcription factors SOX2 and SOX9 are stem cell-associated markers while the pituitary progenitor marker PROP1 is involved in anterior pituitary development. We characterised the presence of these markers known to be present in the human pituitary in non-functioning (NF) PitNETs. : We investigated the pituitary transcription factors SOX2, SOX9 and PROP1 by immunohistochemistry (IHC) (N = 125) and RT-qPCR (N = 78) in a retrospective cohort of clinically NF-PitNETs. The markers were scored based on the percentage of immunolabeled cells. IHC staining scores were compared to reintervention rates for the whole cohort, and to expression of FSH, LH or ER in gonadotroph NF-PitNETs. : Most tumours showed no or few cells positive for SOX2, SOX9 and PROP1. More patients with SOX2-negative tumours went through reintervention (40 % vs 19 %, p = 0.03). SOX2, SOX9 and PROP1 staining correlated positively to each other (SOX2 and SOX9 r = 0.666, SOX2 and PROP1 r = 0.704, SOX9 and PROP1 r = 0.570, and p < 0.001 for all). In gonadotroph NF-PitNETs, staining for SOX2 and PROP1 was positively associated to FSHβ staining (p < 0.001 for both). Staining for SOX2, SOX9 and PROP1 was positively associated with gene expression of Estrogen Receptor 1 (ESR1) (p < 0.001, p = 0.004 and p < 0.001) and IHC staining for ERα (p = 0.001, p = 0.03 and p = 0.05, respectively). : SOX2, SOX9 and PROP1 were present at low levels in NF-PitNETs. Absence of SOX2 staining was associated with a higher reintervention rate. The stem cell markers correlated positively with markers of gonadotroph differentiation in gonadotroph NF-PitNETs. SOX2 and SOX9 were frequently coexpressed and showed positivity in intratumoural cells with epithelial features, however without coexpression of pituitary transcription factors.
PubMed: 38845811
DOI: 10.17879/freeneuropathology-2024-5396 -
Nature Reviews. Endocrinology Jun 2024Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common... (Review)
Review
Acromegaly is a rare endocrine disease caused by hypersecretion of growth hormone, most commonly arising due to a pituitary adenoma. Diabetes mellitus is a common complication of acromegaly, occurring in approximately one-third of patients. The risk of diabetes mellitus in acromegaly is driven by increased exposure to growth hormone, which directly attenuates insulin signalling and stimulates lipolysis, leading to decreased glucose uptake in peripheral tissues. Acromegaly is a unique human model, where insulin resistance occurs independently of obesity and is paradoxically associated with a lean phenotype and reduced body adipose tissue mass. Diabetes mellitus in patients with acromegaly is associated with an increased risk of cardiovascular morbidity and mortality. Therefore, preventive measures and optimized treatment of diabetes mellitus are essential in these patients. However, specific recommendations for the management of diabetes mellitus secondary to acromegaly are lacking due to limited research on this subject. This Review explores the underlying mechanisms for diabetes mellitus in acromegaly and its effect on morbidity and mortality. We also discuss treatment modalities for diabetes mellitus that are suited for patients with acromegaly. Improved understanding of these issues will lead to better management of acromegaly and its associated metabolic complications.
PubMed: 38844688
DOI: 10.1038/s41574-024-00993-x -
Acta Neurochirurgica Jun 2024An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary...
BACKGROUND
An ACTH-secreting pituitary adenoma is the most common cause of excessive endogenous glucocorticoid production resulting in Cushing's Syndrome. A multidisciplinary approach is paramount. Selective adenomectomy is the treatment of choice.
METHOD
Endoscopic transnasal transsphenoidal approach to the tumour, along with techniques for resection, are demonstrated.
CONCLUSION
Endoscopic transsphenoidal approaches with its magnified view of the pituitary gland allows precise microsurgical dissection during selective adenomectomy. This technique increases the possibility of proving a gross total resection, leading to clinical and biochemical cure in these patients.
Topics: Humans; Adenoma; Pituitary ACTH Hypersecretion; Endoscopy; ACTH-Secreting Pituitary Adenoma; Pituitary Neoplasms; Neuroendoscopy; Treatment Outcome; Neurosurgical Procedures; Female; Sphenoid Bone
PubMed: 38842720
DOI: 10.1007/s00701-024-06078-y -
Expert Review of Endocrinology &... Jul 2024Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line... (Review)
Review
INTRODUCTION
Acromegaly is a rare endocrine disorder usually caused by a benign growth hormone‒secreting pituitary adenoma. Surgical adenoma resection is typically the first line of treatment, and medical therapy is used for patients with persistent disease following surgery, for adenoma recurrence, or for patients ineligible for, or declining, surgery. Approved somatostatin receptor ligands (SRLs) have been limited to injectable options, until recently. Oral octreotide capsules (OOC) are the first approved oral SRL for patients with acromegaly.
AREAS COVERED
We review published reports and provide case study examples demonstrating practical considerations on the use of OOC. Using two hypothetical case scenarios, we discuss current treatment patterns, breakthrough symptoms and quality of life (QoL), efficacy of SRLs, OOC dose titration, evaluation of OOC treatment response, and incidence and management of adverse events.
EXPERT OPINION
OOC are an option for patients with acromegaly including those who experience breakthrough symptoms, who have preference for oral therapies, or other reasons for declining injectable SRLs. OOC have been associated with improved patient-reported QoL measures compared with those reported for lanreotide and octreotide. Continued real-world experience will determine whether OOC, alone or in combination with other therapies, provides further advantages over current injectable acromegaly treatments.
Topics: Humans; Acromegaly; Octreotide; Administration, Oral; Antineoplastic Agents, Hormonal; Quality of Life; Capsules; Adenoma; Growth Hormone-Secreting Pituitary Adenoma; Clinical Trials as Topic; Treatment Outcome
PubMed: 38842362
DOI: 10.1080/17446651.2024.2363540 -
Frontiers in Surgery 2024Hemangiopericytoma (HPC) constitutes less than 1% of all primary central nervous system tumors. It is a vascular neoplasm with potential malignancy that, in rare...
UNLABELLED
Hemangiopericytoma (HPC) constitutes less than 1% of all primary central nervous system tumors. It is a vascular neoplasm with potential malignancy that, in rare instances, manifests as a primary lesion within the brain. Typically, it originates from the meninges. Here, we describe an exceptionally uncommon sellar region solitary fibrous tumor/hemangiopericytoma (SFT/HPC) that mimicked a nonfunctional pituitary adenoma.
CASE PRESENTATION
A 54-year-old male was referred to our hospital due to progressive blurred vision in the left eye over the past year. A homogeneous iso-dense extra-axial intrasellar round mass with extension into the suprasellar region, mainly on the left side, along with bony erosion and osteolysis around the sellar region, was observed on a brain computed tomography (CT) scan. Brain magnetic resonance imaging (MRI) revealed a well-defined 251,713 mm mass with iso-signal on T1-weighted images and hypersignal on T2-weighted images, originating from the pituitary gland within the sella turcica. The mass avidly enhanced following Gadolinium injection and adhered to both carotid arteries without vascular compression or invasion. It extended to the suprasellar cistern and compressed the optic chiasm. The diagnosis was nonfunctional pituitary macroadenoma, leading to the decision for Endoscopic Trans-Sphenoidal Surgery (ETSS). A non-sustainable, soft, grayish mass was grossly and totally resected during the operation. Subsequently, there was a significant improvement in visual acuity during the early postoperative period. Histopathologic examination confirmed hemangiopericytoma (WHO grade II).
CONCLUSION
Due to its malignant nature, hemangiopericytoma should be included in the differential diagnosis of a sellar mass, both from a clinical and morphological perspective.
PubMed: 38840972
DOI: 10.3389/fsurg.2024.1359787 -
Surgical Neurology International 2024Chordomas are rare, locally aggressive neoplasms recognized as derivatives of the notochord vestiges. These tumors typically involve the midline axial skeleton, and...
BACKGROUND
Chordomas are rare, locally aggressive neoplasms recognized as derivatives of the notochord vestiges. These tumors typically involve the midline axial skeleton, and intracranial chordomas exhibit proclivity for the spheno-occipital region. However, purely intrasellar occurrences are extremely rare. We report a case of intrasellar chordoma, which masqueraded as a pituitary neuroendocrine tumor.
CASE DESCRIPTION
An 87-year-old female presented with an acutely altered mental state after a few-week course of headaches and decreased left vision. Adrenal insufficiency was evident, and magnetic resonance imaging revealed an intrasellar lesion with heterogeneous contrast enhancement and marked T2 hyperintensity. Central adrenal insufficiency due to an intrasellar lesion was suspected. Cortisol replacement was initiated, and transsphenoidal surgery was performed. Anterosuperior displacement of the normal pituitary gland and the absence of the bony dorsum sellae were notable during the procedure. Histological examination led to a diagnosis of conventional chordoma, and upfront adjuvant stereotactic radiosurgery was executed. She has been free from tumor progression for 12 months.
CONCLUSION
This case and literature review suggested that the pathognomonic features of intrasellar chordoma were heterogeneous contrast enhancement, marked T2 hyperintensity, osteolytic destruction of the dorsum sellae, and anterosuperior displacement of the pituitary gland. Clinical outcomes seemed slightly worse than those of all skull base chordomas, which were the rationale for upfront radiosurgery in our case. Neurosurgeons should include intrasellar chordomas in the differential diagnosis of intrasellar lesions, carefully dissect them from the adjacent critical anatomical structures, and consider upfront radiosurgery to achieve optimal patient outcomes.
PubMed: 38840611
DOI: 10.25259/SNI_116_2024 -
AJR. American Journal of Roentgenology Jun 2024
PubMed: 38838233
DOI: 10.2214/AJR.24.31418 -
Journal of Neurological Surgery Reports Apr 2024This article aims to identify patient- and surgery-related factors that could predict the development of postoperative central diabetes insipidus (DI). This is a...
This article aims to identify patient- and surgery-related factors that could predict the development of postoperative central diabetes insipidus (DI). This is a retrospective case-control study conducted at a single-institution tertiary referral center. Patients undergoing endoscopic endonasal skull base surgery for pituitary adenoma between November 2018 and April 2023 were recruited. The main outcome measures collected include age, gender, comorbidities, tumor type, postoperative DI, intraoperative and postoperative cerebrospinal fluid (CSF) leak, flow of CSF leak, number of layers required for repair, the use of nasal packing, and hospital length of stay. A total of 20 patients developed DI postoperatively. Patients' demographic and comorbidity profile did not correlate with DI development. The encounter of an intraoperative CSF leak was correlated with postop DI (chi-square (1) = 18.35, < 0.001) with a relative risk (RR) of 2.7 (confidence interval [CI] = 1.37-5.28). The use of nasal packs was also correlated with postop DI (chi-square (1) = 10.17, = 0.001) with a RR of 1.8 (CI = 1.15-2.87). Defects requiring a two or more layers for reconstruction also correlated with postop DI compared to single layer repairs (chi-square (1) = 12.15, < 0.001) irrelevant of the materials used. Development of DI postop correlated with an increased hospital length of stay ( (64) = -3.35, = 0.001). The physician should be careful when evaluating patients with pituitary adenomas in the postoperative period, particularly those with intraoperative CSF leak, nasal packing, and those who underwent multilayer reconstruction of the surgical defect.
PubMed: 38835396
DOI: 10.1055/a-2324-1303