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Radiology Case Reports Sep 2022Primary intracranial germ cell tumors are rare, often affecting children and young patients. Germinomas are the most common type of germ cell tumors. We present the case...
Primary intracranial germ cell tumors are rare, often affecting children and young patients. Germinomas are the most common type of germ cell tumors. We present the case of a 10-year-old child, who was admitted with decreased visual acuity, asthenia, polyuro-polydipsic syndrome, and gait disorder. His biological assessment showed an hypocortisolemia and diabetes insipidus. Imaging found a bifocal process in the suprasellar and pineal region, suggestive of a bifocal germinoma. Imaging data and the positivity of human chorionic gonadotrophin in the cerebrospinal fluid were in favor of the diagnosis of bifocal germinal tumor confirmed by biopsy. Currently the patient is hospitalized in pediatric oncology department. The diagnosis of germ cell tumors is based on imaging, tumor marker assays, and biopsy. They are treated by radiation therapy alone or in combination with reduction chemotherapy, and surgery for tumor residues. The location of the tumor usually makes surgery difficult.
PubMed: 35755113
DOI: 10.1016/j.radcr.2022.05.080 -
Military Medical Research Sep 2022Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the...
BACKGROUND
Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the oncostatic function of melatonin on esophageal squamous cell carcinoma (ESCC) remains elusive. This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.
METHODS
ESCC cell lines treated with or without melatonin were used in this study. In vitro colony formation and EdU incorporation assays, and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells. RNA-seq, qPCR, Western blotting, recombinant lentivirus-mediated target gene overexpression or knockdown, plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth. IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes' expression and prognosis of ESCC.
RESULTS
Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7 (HDAC7), c-Myc and ubiquitin-specific peptidase 10 (USP10) in ESCC cells (P < 0.05). The expressions of HDAC7, c-Myc and USP10 in tumors were detected significantly higher than the paired normal tissues from 148 ESCC patients (P < 0.001). Then, the Kaplan-Meier survival analyses suggested that ESCC patients with high HDAC7, c-Myc or USP10 levels predicted worse overall survival (Log-rank P < 0.001). Co-IP and Western blotting analyses further revealed that HDAC7 physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription. Notably, our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth, and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells. Additionally, we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.
CONCLUSIONS
Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth, and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
Topics: Animals; Catenins; Cell Proliferation; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Feedback; Histone Deacetylases; Humans; Melatonin; Mice; Mice, Nude; Protein Stability; Proto-Oncogene Proteins c-myc; Ubiquitin Thiolesterase; Ubiquitin-Specific Proteases; beta Catenin
PubMed: 36163081
DOI: 10.1186/s40779-022-00412-0 -
Cancers Mar 2021The pineal gland is a small, pinecone-shaped endocrine gland that participates in the biological rhythm regulation of vertebrates. The recognized major product of the... (Review)
Review
The pineal gland is a small, pinecone-shaped endocrine gland that participates in the biological rhythm regulation of vertebrates. The recognized major product of the pineal gland is melatonin-a multifunctional endogenous indoleamine. Accumulating evidence suggests that the pineal gland is important for preserving ideal health conditions in vertebrate. Tumors of the pineal region account for approximately 3-11% of pediatric brain neoplasms but fewer than 1% of brain neoplasms in adults. It is fundamental to expand advanced imaging techniques together with both clinical and laboratory knowledge, to help to differentiate among pineal neoplasms and thus facilitate accurate primary diagnoses and proper therapeutic interventions. In this review, we report the gross anatomy of the pineal gland and its functional significance and discuss the clinical relevance of pineal gland tumors, underlining the importance of identifying the leading causes of pineal region masses.
PubMed: 33801639
DOI: 10.3390/cancers13071547 -
Practical Neurology May 2021The widespread use of MRI has led to the increasingly frequent diagnosis of pineal and colloid cysts. While most are small and incidental, do not require long-term... (Review)
Review
The widespread use of MRI has led to the increasingly frequent diagnosis of pineal and colloid cysts. While most are small and incidental, do not require long-term monitoring and will never need treatment, they are a cause of patient anxiety and clinician uncertainty regarding the optimal management-particularly for larger cysts or those with an atypical appearance. Occasionally pineal cysts, and more commonly colloid cysts, cause hydrocephalus that requires urgent neurosurgical treatment. More recently the non-hydrocephalic symptomatic pineal cyst has been described in the neurosurgical literature but there is controversy over this entity and its management. This review addresses the difficulties in managing pineal and colloid cysts and provides a pragmatic framework for the practising clinician.
PubMed: 34039752
DOI: 10.1136/practneurol-2020-002838 -
Aging Nov 2019The inflammatory-associated factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with...
The inflammatory-associated factors interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine (melatonin) is a natural hormone secreted by the pineal gland which has been shown to participate in several physiological and pathological progresses, such as aging, anti-inflammation, anti-apoptosis and autophagy regulation. However, the effects of melatonin on IVD remain unclear. In the present study, we treated human nucleus pulposus cells (NPCs) with melatonin and discovered that melatonin could modulate extracellular matrix (ECM) remodeling induced by IL-1β by enhancing collagen II and aggrecan expression levels and by downregulating matrix metalloproteinase-3 (MMP-3) levels. These findings were verified by western blot and immunofluorescence assays. Intraperitoneal injection of melatonin mitigated IVDD in the rat tail puncture model. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue and Celium red staining methods were adopted to evaluate IVDD grades, the structural integrity of nucleus pulposus (NP) and annulus fibrosus (AF) and the damage and calcification of the cartilage endplate. Melatonin reduced inflammatory cell aggregation and the release of the inflammatory factors IL-1β, IL-6, TNF-α as determined by immunohistochemistry. In conclusion, the present study demonstrated that melatonin could modulate ECM remodeling by IL-1β in vitro and attenuate the IVDD and induction of inflammation in a rat tail puncture model in vivo. The data demonstrated that melatonin may contribute to the restoration processs of IVD following damage and may be used as a potential novel therapy for IVDD.
Topics: Animals; Extracellular Matrix; Female; Humans; Inflammation; Interleukin-1beta; Intervertebral Disc Degeneration; Melatonin; Nucleus Pulposus; Rats; Rats, Sprague-Dawley
PubMed: 31772145
DOI: 10.18632/aging.102472 -
Neuro-oncology Jun 2022The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized...
BACKGROUND
The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3-21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate.
METHODS
Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim.
RESULTS
One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment.
CONCLUSIONS
While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Carboplatin; Child; Child, Preschool; Etoposide; Germinoma; Humans; Pineal Gland; Prospective Studies; Young Adult
PubMed: 34850169
DOI: 10.1093/neuonc/noab270 -
Molecules (Basel, Switzerland) Nov 2017Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as... (Review)
Review
Melatonin is catabolized both enzymatically and nonenzymatically. Nonenzymatic processes mediated by free radicals, singlet oxygen, other reactive intermediates such as HOCl and peroxynitrite, or pseudoenzymatic mechanisms are not species- or tissue-specific, but vary considerably in their extent. Higher rates of nonenzymatic melatonin metabolism can be expected upon UV exposure, e.g., in plants and in the human skin. Additionally, melatonin is more strongly nonenzymatically degraded at sites of inflammation. Typical products are several hydroxylated derivatives of melatonin and ¹-acetyl-²-formyl-5-methoxykynuramine (AFMK). Most of these products are also formed by enzymatic catalysis. Considerable taxon- and site-specific differences are observed in the main enzymatic routes of catabolism. Formation of 6-hydroxymelatonin by cytochrome P subforms are prevailing in vertebrates, predominantly in the liver, but also in the brain. In pineal gland and non-mammalian retina, deacetylation to 5-methoxytryptamine (5-MT) plays a certain role. This pathway is quantitatively prevalent in dinoflagellates, in which 5-MT induces cyst formation and is further converted to 5-methoxyindole-3-acetic acid, an end product released to the water. In plants, the major route is catalyzed by melatonin 2-hydroxylase, whose product is tautomerized to 3-acetamidoethyl-3-hydroxy-5-methoxyindolin-2-one (AMIO), which exceeds the levels of melatonin. Formation and properties of various secondary products are discussed.
Topics: Acetylation; Animals; Catalysis; Humans; Hydroxylation; Melatonin; Metabolic Networks and Pathways
PubMed: 29160833
DOI: 10.3390/molecules22112015 -
Surgical Neurology International 2018Pineal cysts are benign lesions of the pineal gland without a clear etiology. Currently, different approaches are described to deal with pineal region lesions and...
BACKGROUND
Pineal cysts are benign lesions of the pineal gland without a clear etiology. Currently, different approaches are described to deal with pineal region lesions and particularly with pineal cysts. Although endoscopic procedures are becoming more frequent, some technical advantages of the microsurgical resection still make it the gold standard. Our aim was to demonstrate the efficiency and safety of our microsurgical technique into deep brain territories under the principle "simple, clean, and preserving the normal anatomy." Herein, we present an unedited microneurosurgery of a histologically confirmed large benign pineal cyst.
CASE DESCRIPTION
A patient with antidepressant medication, psychotic attacks, memory problems, and progressively intense headache along the last months underwent sitting praying position and supracerebellar infratentorial paramedian approach. Under high magnification, the pineal region was accessed over the right cerebellar hemisphere. A lateral focused opening of the quadrigeminal cistern and the posterior wall of the pineal cyst were followed by partial aspiration of the cystic content. Small vessels running around the cyst were carefully dissected, and few of those attached to the wall were coagulated and cut. After careful devascularization of the lesion, the cyst was detached and pulled out using soft and continuous traction with a long ring microforceps in the right hand and thumb-controlled suction tube in the left one. The final steps included meticulous attention to any bleeding securing complete hemostasis of the surgical site. The postoperative course was uneventful and the patient improved dramatically with resolution of the headache and progressive reduction of psychiatric medication.
CONCLUSION
This unedited video offers all detailed aspects that a neurosurgeon as the senior author JH considers essential when performing an efficient and safe pineal cyst surgery.
VIDEOLINK
http://surgicalneurologyint.com/videogallery/pineal-cyst/.
PubMed: 30687572
DOI: 10.4103/sni.sni_356_18 -
Medicine and Pharmacy Reports Jul 2019The pineal gland is a photo-neuro-endocrine organ situated inside the brain, that secretes serotonin, melatonin and N,N-dymethyltriptamine. This narrative review will... (Review)
Review
INTRODUCTION
The pineal gland is a photo-neuro-endocrine organ situated inside the brain, that secretes serotonin, melatonin and N,N-dymethyltriptamine. This narrative review will address the latest information gathered on this function of the gland as well as the unknown roles it may have. The different histological and pathological findings of the pineal gland have demonstrated a role in clinical manifestations of numerous endocrine, neurological and psychiatric pathologies.
MATERIALS
For this narrative review we used the NCBI website database PubMed. The search terms were "Pineal Gland" AND/OR "histology, melatonin, DMT, pathology". Total number of articles included were 86.
RESULTS
We have reviewed physiological information of melatonin and DMT, anatomical, histological and histopathological information on the pineal gland and its role in endocrine, neurological and psychiatric pathology.
CONCLUSION
The role of melatonin in immunity and its potential therapeutic effects show promising potential for further research. DMT seems to have a role in psychiatric pathology and potential therapeutic effects. Proper tumoral screening and diagnostic protocol are required.
PubMed: 31460502
DOI: 10.15386/mpr-1235