Research status and prospects of pituitary adenomas in conjunction with neurological and psychiatric disorders and the tumor microenvironment.

Patients with pituitary neuroendocrine tumors (PitNETs) often experience neuropsychiatric disorders due to factors such as hormonal imbalances, and inadequate management of medications, surgeries, and radiation therapies. Commonly observed disorders include depression, anxiety, and cognitive dysfunction, which significantly impact patients' quality of life and prognosis. PitNETs have a significant presence of immune cells within the tumor microenvironment (TME), predominantly macrophages and T lymphocytes. These immune cells secrete a variety of cytokines, growth factors, and chemokines, which regulate the biological behaviors of PitNETs, including tumor initiation, proliferation, migration, invasion, and angiogenesis. In addition, this review provides a pioneering summary of the close relationships between the aberrant secretion of proinflammatory cytokines within the TME of PitNETs and the occurrence of neuropsychiatric disorders, along with their potential underlying mechanisms. The cytokines produced as a result of TME dysregulation may affect various aspects of the central nervous system, including neurotransmitter metabolism, neuroendocrine function, and neurovascular plasticity, thereby leading to a higher susceptibility to neurobehavioral disorders in PitNET patients.

Changes in monsoon precipitation in East Asia under a 2°C interglacial warming.

Past intervals of warming provide the unique opportunity to observe how the East Asia monsoon precipitation response happened in a warming world. However, the available evaluations are primarily limited to the last glacial-to-interglacial warming, which has fundamental differences from the current interglacial warming, particularly in changes in ice volume. Comparative paleoclimate studies of earlier warm interglacial periods can provide more realistic analogs. Here, we present high-resolution quantitative reconstructions of temperature and precipitation from north-central China over the past 800 thousand years. We found that the average precipitation increase, estimated by the interglacial data, was only around one-half of that estimated for the glacial-to-interglacial data, which is attributed to the amplification of climate change by ice volume variations. Analysis of the interglacial data suggests an increase in monsoon precipitation of ~100 mm for a warming level of 2°C on the Chinese Loess Plateau.

Endoscopic transcranial transdiaphragmatic approach in a single-stage surgery for giant pituitary adenomas.

Background: The treatment for giant pituitary adenomas (GPAs, maximal diameter >4 cm) remains challenging, with remarkable mortality and morbidity, and there is no consensus on the optimal surgical approach. Gross total resection (GTR) for GPAs is difficult to achieve through a single transsphenoidal or transcranial approach. Any residual tumor is at risk for postoperative apoplexy. In this study, we propose a new surgical technique for resecting the GPAs in a sing-stage transcranial surgery. Methods: A retrospective review of 4 patients with complicated GPAs, who had been treated via an endoscopic transcranial transdiaphragmatic approach in a single-stage surgery after routine transcranial resection, was performed. The following data was analyzed: clinical characteristics, preoperative imaging studies, resection rate, perioperative morbidity and mortality, as well as postoperative outcomes. Results: All patients had nonfunctioning GPAs and preoperative visual disturbances. In three patients, GTR was achieved, and in one patient, near-total resection (90%-100% of the tumor) was achieved. Three patients attained improved postoperative visual function, while one patient's vision remained unchanged. One patient suffered a deficiency in adrenocorticotropic hormone along with thyroid-stimulating hormone, and one patient developed diabetes insipidus. Notably, none of the patients suffered cerebrospinal fluid leakage. However, one patient developed an epidural hematoma and underwent decompressive craniectomy. Conclusions: The endoscopic transcranial transdiaphragmatic approach in a single-stage surgery can be efficiently and safely performed for maximal excision of GPAs with extensive suprasellar extension. Furthermore, relative to the conventional combined or staged approaches, this innovative surgical strategy provides neurosurgeons with a clear operative field with reduced invasiveness.

Overexpression of RAB34 associates with tumor aggressiveness and immune infiltration in glioma.

RAB34 (RAB34, member RAS oncogene family) is aberrantly expressed in various cancers and exhibits oncogenic properties. However, its function in glioma remains largely unclear. In the present study, we collected 697 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset and 325 RNA-seq data from Chinese Glioma Genome Atlas (CGGA) dataset. Bioinformatics and PCR analysis showed that RAB34 expression was positively related to the glioma tumor grade and predicted poor outcomes for glioma patients. Additionally, RAB34 expression was significantly up-regulated in classical and mesenchymal subtypes, and isolated diastolic hypertension wild-type gliomas. Moreover, RAB34 expression was remarkably correlated with inflammatory activities, immune infiltration, and immune checkpoints in glioma. In vitro experiments demonstrated that inhibition of RAB34 restrained the growth, migration, as well as invasion of glioma cells, and reversed the epithelial-to-mesenchymal transition (EMT) process. Our findings established RAB34 as a novel progression-related biomarker and a possible immunotherapy target for glioma.

Epigenetic Activation of lncRNA MIR155HG Mediated by Promoter Hypomethylation and SP1 is Correlated with Immune Infiltration in Glioma.

Purpose: The lncRNA MIR155 host gene (MIR155HG) plays a role in the progression of several malignant cancers. However, the specific mechanisms of MIR155HG in glioma progression have not been clearly established. The purpose of this study was to investigate the function of MIR155HG in glioma at the transcriptome level and relationship with immune infiltration. Patients and Methods: Totally, 697 RNA-seq and 594 DNA methylation data were retrieved from The Cancer Genome Atlas (TCGA) dataset while 325 RNA-seq data were retrieved from the Chinese Glioma Genome Atlas (CGGA) dataset. The DNA methylation levels of MIR155HG CpG islands were assessed through bisulfite amplicon sequencing (BSAS). The regulatory mechanism of SP1 on MIR155HG was examined by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. R language was used as the main tool for statistical analysis and graphical work. Results: MIR155HG was predominantly expressed in the isocitrate dehydrogenase (IDH) wild-type as well as mesenchymal subtype gliomas. Promoter methylation levels of MIR155HG in glioblastoma (GBM) were remarkably decreased compared with those in lower-grade glioma (LGG). In addition, there were negative correlations between promoter methylation levels and MIR155HG expressions but positive correlations with patients' overall survival. In vitro studies further revealed that MIR155HG expression was regulated by DNA promoter methylation and transcription factor (SP1) binding to the promoter. Moreover, there was a close association between MIR155HG expression and immune as well as stromal cell infiltrations, inflammatory activities, and immune checkpoints. Clinically, univariate and multivariate Cox analyses revealed that MIR155HG is an independent prognostic marker for glioma patients. Conclusion: Our results established that MIR155HG is a potential biomarker for prognosis and an immunotherapeutic target in glioma.

Large-Scale Analysis Reveals the Specific Clinical and Immune Features of DGCR5 in Glioma.

PURPOSE: Long non-coding RNA DGCR5 plays different roles in different types of cancer. The purpose of this study was to investigate the clinicopathological features, potential biological functions and prognostic significance of DGCR5 in glioma in a large-scale study. MATERIALS AND METHODS: A total of 697 RNA-seq data from The Cancer Genome Atlas (TCGA) and 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) were enrolled in this study. R language was used as the main tool for statistical analysis and graphical work. RESULTS: DGCR5 showed a negative correlation with the WHO grade of malignancy in glioma. Specifically, DGCR5 expression was significantly decreased in GBM and IDH wild-type glioma. Gene ontology analysis showed that DGCR5 was predominantly enriched in immune-related biological processes. Additionally, DGCR5 showed a significant correlation with stromal and immune cell populations, inflammatory activities and immune checkpoints. Clinically, patients with low-expression level of DGCR5 exhibited a worse overall survival. CONCLUSION: DGCR5 expression is downregulated in glioma, and low DGCR5 independently predicts worse prognosis in glioma patients. Moreover, DGCR5 is significantly associated with immune response and immune infiltration. These findings suggest that DGCR5 is a promising immunotherapy target and a novel prognostic biomarker for glioma.

DACH1 inhibits glioma invasion and tumor growth via the Wnt/catenin pathway.

BACKGROUND/AIM: Glioma is the most common and malignant nervous system tumor and is associated with high-grade malignancy and high recurrence. The mammalian Dachshund1 (DACH1) is a recognized anti-tumor site and has low expression in several malignant tumors, including glioma. We designed and conducted this study to further determine the mechanism of DACH1 in glioma. PATIENTS AND METHODS: The data collected from specimens of patients with glioma from GSE16011 and REMBRANDT databases were analyzed. The effect of DACH1 on proliferation, migration, and invasion of U87 and U251 cell lines was analyzed in vitro. The symbol targets of the Wnt/ß-catenin pathway were also evaluated through Western blot. RESULTS: DACH1 deficiency was found in glioma tissues, and the DACH1 level was negatively correlated with the tumor malignancy. DACH1 overexpression inhibited the tumor proliferation, migration, and invasion. High expression of DACH1 also dampened the Wnt/ß-catenin pathway, and the activation of the Wnt/ß-catenin pathway partly led to the limited proliferation in glioma cells. CONCLUSION: Downregulation of DACH1 was related to the malignancy and poor prognosis of patients with glioma, and DACH1 overexpression inhibited the tumor proliferation via the Wnt/ß-catenin pathway. These findings might assist in the discovery of novel potential diagnostic and therapeutic targets for DACH1, thereby reducing the malignancy and recurrence of glioma.

Moesin Up-regulation Is Associated with Enhanced Tumor Progression Imaged Non-invasively in an Orthotopic Mouse Model of Human Glioblastoma.

BACKGROUND/AIM: Glioblastoma is a recalcitrant and poorly understood disease. The aim of the present study was to investigate the effect of moesin up-regulation on tumor progression in an orthotopic nude-mouse model of human glioblastoma. MATERIALS AND METHODS: U87-GFP glioblastoma cells, transfected with either U87-H4645 (moesin up-regulated) or U87-H149 (vector control) were orthotopically implanted into the brains of nude mice. Moesin expression in the tumors was analyzed with RT-PCR and western blotting. Real-time fluorescence imaging was used to longitudinally and non-invasively quantitate tumor growth. The expression of cancer-related genes ß-catenin, CD44, MMP-2, ICAM-1, and PCNA in the tumor was analyzed by RT-PCR, western blotting and immunohistochemistry in both sublines. RESULTS: The expression levels of moesin mRNA and protein were significantly increased in the glioblastoma derived from transfected U87-H4645 cells compared to the vector control and untransfected cells. Tumor growth rate and final tumor weight were significantly increased in the animals with the glioblastoma derived from transfected U87-H4645 cells, compared to untransfected and vector control (p<0.01). mRNA expression of ß-catenin, CD44, ICAM-1, and MMP-2 in the glioblastoma derived from the transfected U87-H4645 tumors was significantly increased compared with tumors derived from untransfected and vector-control U87 cells (p<0.01). Furthermore, a similar increase in the expression of these proteins was observed by western blotting or immunohistochemistry. CONCLUSION: Up-regulation of moesin expression in glioblastoma cells resulted in more aggressive orthotopic glioblastoma growth in nude mice. This effect may be mediated by the regulation of several proliferation-, adhesion-, and invasion-related cancer genes, which may serve as future therapeutic targets for this recalcitrant disease.

Moesin Expression Is Associated with Glioblastoma Cell Proliferation and Invasion.

AIM: To investigate the effect of moesin expression on cell proliferaton and invasion of human glioblastoma cell lines in vitro. MATERIALS AND METHODS: Glioblastoma LN229 and U87 cells were transfected with the H4645-plenti-EGFP-moesin expression vector for moesin up-regulation. Moesin and ß-catenin expression levels in the transfected cells were analyzed by real-time polymerase chain reaction (PCR) and Western blotting. Cell proliferation was measured using the CCK8 assay. Cell invasion and migration ability were assessed using a transwell cell invasion and wound-healing assay. RESULTS: Moesin mRNA and protein expression were significantly increased in the two transfected LN229-H4645 and U87-H4645 cell lines. ß-catenin expression was increased by moesin up-regulation in the transfected LN229-H4645 and U87-H4645 cell lines. The CCK-8 assay revealed that up-regulating moesin results in a significant increase in glioblastoma cell proliferation. Glioblastoma cell invasion and migration were increased by moesin up-regulation. CONCLUSION: Up-regulation of moesin expression in glioblastoma cells correlated with increases in cell proliferation, invasion and migration, suggesting moesin's role in glioblastoma progression.

Blocking MIR155HG/miR-155 axis inhibits mesenchymal transition in glioma.

BACKGROUND: MIR155 host gene (MIR155HG) is a long noncoding RNA that has been considered as the primary micro (mi)RNA of miR-155. MIR155HG plays an essential role in hematopoiesis, inflammation, and tumorigenesis. Our study investigated the clinical significance, biological function, mechanisms, and small-molecule inhibitors of the MIR155HG/miR-155 axis in glioma. METHODS: We analyzed the expression of the MIR155HG/miR-155 axis and the correlation with glioma grade and patient survival using 2 different glioma gene expression datasets. Biological significance was elucidated through a series of in vitro and in vivo experiments. Furthermore, we conducted a high-throughput screening for small molecules to identify a potential inhibitor of the MIR155HG/miR-155 axis. RESULTS: Increased MIR155HG was associated with glioma grade, mesenchymal transition, and poor prognosis. Functionally, MIR155HG reduction by small interfering RNA inhibited cell proliferation, migration, invasion, and orthotopic glioma growth by repressing the generation of its derivatives miR-155-5p and miR-155-3p. Bioinformatics and luciferase reporter assays revealed that protocadherin 9 and protocadherin 7, which act as tumor suppressors by inhibiting the Wnt/ß-catenin pathway, were direct targets of miR-155-5p and miR-155-3p, respectively. Finally, we identified NSC141562 as a potent small-molecule inhibitor of the MIR155HG/miR-155 axis. CONCLUSIONS: Our results demonstrate that the MIR155HG/miR-155 axis plays a critical role in facilitating glioma progression and serves as a prognostic factor for patient survival in glioblastoma. High-throughput screening indicated that the MIR155HG/miR-155 axis inhibitor NSC141562 may be a useful candidate anti-glioma drug.

Serum microRNA-128 as a biomarker for diagnosis of glioma.

MicroRNA-128 is down-regulated in glioma tissues, which regulates cell proliferation, self-renewal, apoptosis, angiogenesis and differentiation. This study aims at investigating the diagnostic value of serum miR-128 in human glioma. Real-time quantitative reverse transcriptase polymerase chain reaction was used to detect the expression levels of miR-128 in serum samples from 151 glioma patients, 59 postoperative patients, 52 meningioma patients and 53 normal donors. To analyze the association of miR-128 expression with clinicopathological parameters in serum samples and matched tissues, matched 151 glioma tissues were collected in the study. Receiver operating characteristic analysis (ROC) was utilized to evaluate the value of serum miR-128 as a biomarker for the early diagnosis of glioma. Results revealed that miR-128 expression was significantly decreased in glioma preoperative serum compared with normal controls and meningioma serum samples (both P < 0.001). ROC analyses showed that serum miR-128 levels were reliable in distinguishing patients with glioma from normal controls and meningioma, with the area under the curve (AUC) values of 0.9095 and 0.8283, respectively. In addition, the AUC value for discriminating glioma II-IV from I was 0.7362. Importantly, serum miR-128 expression was significantly elevated after surgery (P < 0.001), although it didn't reach to normal levels (P < 0.001). Furthermore, low miR-128 levels in serum and tissue were markedly correlated with high pathological grade and low Karnofsky Performance Status score (KPS). These findings proved that serum miR-128 could be a sensitive and specific biomarker of glioma.