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Folia Neuropathologica 2023BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain...
BCOR is expressed in a new brain tumour entity, i.e. 'CNS tumour with BCOR internal tandem duplication' (HGNET BCOR) but not in several other high grade paediatric brain tumours investigated. Immunohistochemical detection of BCOR expression may therefore serve as a potential diagnostic marker. Nevertheless, in rare paediatric glioma cases recurrent EP300-BCOR fusions were detected, which resulted in strong BCOR immunopositivity. We have therefore examined other, not analysed so far, types of central nervous system (CNS) tumours, pineoblastoma and germinoma, to assess a potential involvement of BCOR in these tumours. Levels of BCOR RNA expression were investigated by NanoString nCounter system analysis in a series of altogether 66 high grade paediatric tumours, including four pineoblastoma cases. Immunohistological detection of BCOR was performed in eight pineoblastoma, five germinoma and four atypical teratoid rhabdoid tumours (ATRTs), all located in the pineal region. We detected BCOR expression in all pineoblastomas, at the RNA and protein levels, but not in germinomas and ATRTs. Further analysis of pineoblastoma samples did not reveal the presence of either BCOR internal tandem duplication or BCOR fusion involvement. Positive immunohistological BCOR nuclear reaction in pineoblastoma may therefore differentiate this type of tumour from other high grade tumours located in the pineal region.
Topics: Humans; Child; Pinealoma; Brain Neoplasms; Germinoma; RNA; Rhabdoid Tumor; Pineal Gland; Proto-Oncogene Proteins; Repressor Proteins
PubMed: 37587886
DOI: 10.5114/fn.2023.129377 -
Cell Communication and Signaling : CCS Mar 2021Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen... (Review)
Review
Prostate cancer (PCa) is one of the most commonly diagnosed human cancers in males. Nearly 191,930 new cases and 33,330 new deaths of PCa are estimated in 2020. Androgen and androgen receptor pathways played essential roles in the pathogenesis of PCa. Androgen depletion therapy is the most used therapies for primary PCa patients. However, due to the high relapse and mortality of PCa, developing novel noninvasive therapies have become the focus of research. Melatonin is an indole-like neurohormone mainly produced in the human pineal gland with a prominent anti-oxidant property. The anti-tumor ability of melatonin has been substantially confirmed and several related articles have also reported the inhibitory effect of melatonin on PCa, while reviews of this inhibitory effect of melatonin on PCa in recent 10 years are absent. Therefore, we systematically discuss the relationship between melatonin disruption and the risk of PCa, the mechanism of how melatonin inhibited PCa, and the synergistic benefits of melatonin and other drugs to summarize current understandings about the function of melatonin in suppressing human prostate cancer. We also raise several unsolved issues that need to be resolved to translate currently non-clinical trials of melatonin for clinic use. We hope this literature review could provide a solid theoretical basis for the future utilization of melatonin in preventing, diagnosing and treating human prostate cancer. Video abstract.
Topics: Apoptosis; Humans; Male; Melatonin; Models, Biological; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction
PubMed: 33722247
DOI: 10.1186/s12964-021-00723-0 -
Contrast Media & Molecular Imaging 2022Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and... (Review)
Review
Tumors in the pineal region are deep, with complex surrounding anatomy, adjacent to important blood vessels and nerve structures, and surgical resection is difficult and risky. In this paper, we reviewed the literature to understand the epidemiology and clinical manifestations of pineal region tumors in the country and study the clinical indications, related problems, and successful experiences of patients with pineal region tumors treated by the transtentorial-superior approach. The clinical data of 80 patients with pineal region tumors were selected as the retrospective research objects and divided into the control group and the treatment group, with 40 cases in each group, according to the random number table method. The control group was treated using the endoscopic transtentorial approach (Poppen approach), while the treatment group was treated with the endoscopic supratentorial approach (Krause approach). The inflammatory factors, inflammatory stress response, postoperative neurological dysfunction, clinical efficacy, and poor prognosis were observed and compared between the two groups. Tumor resection and recurrence were used to compare the clinical outcomes of tumors in the pineal region. The extent of surgical resection was 100% higher in both groups, and the treatment group was comparable to the control group. The prognosis of patients after the operation was poor. Nausea and vomiting, visual disturbance, upper vision paralysis, and ataxia in the treatment group were significantly lower than those in the control group, with no statistical significance ( > 0.05). At the same time, the bone window can be reduced to reduce trauma and provide a certain reference for patients to choose a safe and complete resection method.
Topics: Brain Neoplasms; Case-Control Studies; Cerebellum; Humans; Pineal Gland; Pinealoma; Retrospective Studies; Treatment Outcome
PubMed: 36017015
DOI: 10.1155/2022/5702309 -
Frontiers in Oncology 2023The diencephalon is a complex midline structure consisting of the hypothalamus, neurohypophysis, subthalamus, thalamus, epithalamus, and pineal body. Tumors arising from... (Review)
Review
The diencephalon is a complex midline structure consisting of the hypothalamus, neurohypophysis, subthalamus, thalamus, epithalamus, and pineal body. Tumors arising from each of these diencephalic components differ significantly in terms of biology and prognosis. The aim of this comprehensive review is to describe the epidemiology, clinical symptoms, imaging, histology, and molecular markers in the context of the . We will also discuss the current management of each of these tumors.
PubMed: 37519792
DOI: 10.3389/fonc.2023.1180267 -
Hormone and Metabolic Research =... Jun 2024Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1... (Review)
Review
Melatonin (5-methoxy-acetyl tryptamine) is a sleep-inducing hormone, and the pineal gland produces it in response to the circadian clock of darkness. In the body, MT1 and MT2 receptors are mostly found, having an orthosteric pocket and ligand binding determinants. Melatonin acts by binding on melatonin receptors, intracellular proteins, and orphan nuclear receptors. It inhibits adenyl cyclase and activates phospholipase C, resulting in gene expression and an intracellular alteration environment. Melatonin signaling pathways are also associated with other intracellular signaling pathways, i. e., cAMP/PKA and MAPK/ERK pathways. Relative expression of different proteins depends on the coupling profile of G protein, accounting pharmacology of the melatonin receptor bias system, and mediates action in a Gi-dependent manner. It shows antioxidant, antitumor, antiproliferative, and neuroprotective activity. Different types of melatonin agonists have been synthesized for the treatment of sleeping disorders. Researchers have developed therapeutics that target melatonin signaling, which could benefit a wide range of medical conditions. This review focuses on melatonin receptors, pharmacology, and signaling cascades; it aims to provide basic mechanical aspects of the receptor's pharmacology, melatonin's functions in cancer and neurodegenerative diseases, and any treatments and drugs designed for these diseases. This will allow a basic comparison between the receptors in question, highlighting any parallels and differences that may exist and providing fundamental knowledge about these receptors to future researchers.
Topics: Humans; Melatonin; Signal Transduction; Animals; Receptors, Melatonin; Neoplasms; Neurodegenerative Diseases
PubMed: 38081221
DOI: 10.1055/a-2226-3971 -
BMC Pediatrics Aug 2023Migraine and tension-type headache are common primary headaches in children. There is a risk of developing secondary headache in children. The current study was aimed to...
PURPOSE
Migraine and tension-type headache are common primary headaches in children. There is a risk of developing secondary headache in children. The current study was aimed to evaluate magnetic resonance imaging findings (MRI) in children with migraine or tension-type headache.
METHODS
The study was planned in children with migraine or tension-type headaches who have been followed up in the pediatric neurology outpatient clinic with regular office visits for at least two years and had neuroimaging in the last year.
RESULTS
280 patients (187 female patients) datas were studied. 91 (61 female patients) were followed up with the diagnosis of migraine and 189 (126 female patients) with the diagnosis of tension-type headaches. The age of patients was found to be 13.1 ± 3.4 years. Brain tumor was found in one child with tension-type headache who had papilledema. Incidental MRI findings found 7.7% and 12.7% in migraine and tension-type headache, respectively. MRI findings in the study were arachnoid cyst (14), pituitary adenoma (6), mega cisterna magna (6), pineal cyst (3), non-specific gliosis (2) and tumor (1).
CONCLUSION
Arachnoid cysts were found incidental as the most common MRI finding in children with migraine or tension-type headache. The rare life-threatening secondary headache may develop in children. The fundus examination as a complement to the neurological examination can be useful for requesting MRI.
Topics: Child; Humans; Female; Adolescent; Tension-Type Headache; Migraine Disorders; Headache; Magnetic Resonance Imaging; Neuroimaging; Brain Neoplasms
PubMed: 37649015
DOI: 10.1186/s12887-023-04264-y -
Brain Research Jul 2016The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER).... (Review)
Review
The Unfolded Protein Response (UPR) is an adaptive cellular program used by eukaryotic cells to cope with protein misfolding stress in the Endoplasmic Reticulum (ER). During tumor development, cancer cells are facing intrinsic (oncogene activation) and extrinsic (limiting nutrient or oxygen supply; exposure to chemotherapies) challenges, with which they must cope to survive. Primary brain tumors are relatively rare but deadly and present a significant challenge in the determination of risk factors in the population. These tumors are inherently difficult to cure because of their protected location in the brain. As such surgery, radiation and chemotherapy options carry potentially lasting patient morbidity and incomplete tumor cure. Some of these tumors, such as glioblastoma, were reported to present features of ER stress and to depend on UPR activation to sustain growth, but to date there is no clear general representation of the ER stress status in primary brain tumors. In this review, we describe the key molecular mechanisms controlling the UPR and their implication in cancers. Then we extensively review the literature reporting the status of ER stress in various primary brain tumors and discuss the potential impact of such observation on patient stratification and on the possibility of developing appropriate targeted therapies using the UPR as therapeutic target.
Topics: Animals; Brain Neoplasms; Cerebellar Neoplasms; Choroid Plexus Neoplasms; Endoplasmic Reticulum Stress; Glioblastoma; Humans; Medulloblastoma; Meningeal Neoplasms; Meningioma; Pineal Gland; Pinealoma; Signal Transduction; Unfolded Protein Response
PubMed: 27016056
DOI: 10.1016/j.brainres.2016.03.015 -
Journal of Pineal Research Aug 2021Hypoxia-inducible factor-1 (HIF-1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor...
Hypoxia-inducible factor-1 (HIF-1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor angiogenesis. Melatonin, also known as N-acetyl-5-methopxytryptamine, is produced naturally by the pineal gland and has anti-angiogenic effects in cancer through its ability to modulate HIF-1α activity. However, the use of melatonin as a therapeutic is limited by its low oral bioavailability and short half-life. Here, we synthesized melatonin-like molecules with enhanced HIF-1α targeting activity and less toxicity and investigated their effects on tumor growth and angiogenesis, as well as the underlying molecular mechanisms. Among melatonin derivatives, N-butyryl-5-methoxytryptamine (NB-5-MT) showed the most potent HIF-1α targeting activity. This molecule was able to (a) reduce the expression of HIF-1α at the protein level, (b) reduce the transcription of HIF-1α target genes, (c) reduce reactive oxygen species (ROS) generation, (d) decrease angiogenesis in vitro and in vivo, and (e) suppress tumor size and metastasis. In addition, NB-5-MT showed improved anti-angiogenic activity compared with melatonin due to its enhanced cellular uptake. NB-5-MT is thus a promising lead for the future development of anticancer compounds with HIF-1α targeting activity. Given that HIF-1α is overexpressed in the majority of human cancers, the melatonin derivative NB-5-MT could represent a novel potent therapeutic agent for cancer.
Topics: Angiogenesis Inhibitors; Animals; Cells, Cultured; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Melatonin; Mice; Mice, Inbred C57BL; Xenograft Model Antitumor Assays; Zebrafish
PubMed: 33955074
DOI: 10.1111/jpi.12739 -
Cancer Letters Apr 2023Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for...
Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE) samples of non-small cell lung cancers (NSCLC, 65), colorectal cancers (CRC, 61), thyroid carcinomas (THCA, 14), gastric cancers (GC, 2), gastrointestinal stromal tumors (GIST, 11), and malignant melanomas (MM, 6). Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients. In vivo experiments demonstrated that the Mitogen-Activated Protein Kinase (MEK) inhibitor could block lung tumor growth in mice with overexpression of Map2k1 protein. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.
Topics: Animals; Mice; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutation; Gastrointestinal Stromal Tumors; Melanoma; High-Throughput Nucleotide Sequencing
PubMed: 36907503
DOI: 10.1016/j.canlet.2023.216123 -
Surgical Neurology International 2022The management of complicated symptomatic pineal cysts in the pediatric population is challenging and variable. Surgical management may include treatment of...
BACKGROUND
The management of complicated symptomatic pineal cysts in the pediatric population is challenging and variable. Surgical management may include treatment of hydrocephalus alone, or direct treatment of the cyst with or without direct hydrocephalus management. This is typically done through craniotomy-based microsurgical approaches to the pineal region or an endoscopic transventricular approach.
METHODS
We present a stepwise minimally invasive technique to treat complicated pineal cysts in young children associated with an obstructive hydrocephalus in a single procedure through third ventriculostomy combined with an intraventricular marsupialization of the pineal cyst through a single burr-hole using stereotactic navigation.
RESULTS
Two young patients with over 2 years of follow-up have done well without complication using this technique. Other literature reports for complex pineal cysts in pediatric patients are reviewed and this technique is not previously described for this population.
CONCLUSION
Endoscopic third ventriculostomy and cyst marsupialization using a single burr-hole and stereotactic navigation for symptomatic or enlarging pineal cysts in children allow for minimally invasive management, a rapid recovery, short hospital stay, and durable outcome owed to redundant CSF flow pathways.
PubMed: 35855169
DOI: 10.25259/SNI_302_2022