Astrocyte elevated gene-1 serves as a target of miR542 to promote glioblastoma proliferation and invasion.

BACKGROUND: Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle. METHODS: The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored. RESULTS: MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT. CONCLUSION: The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression.

BACKGROUND: Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of tripartite motif-containing 24 (TRIM24) in GSCs. METHODS: Immunofluorescence, flow cytometry, and western blot analyses were used to evaluate TRIM24 and cluster of differentiation (CD)133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients' tumors, as measured by both immunohistochemistry and western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion, and xenograft immunohistochemistry were conducted to determine GBM cell invasion. RESULTS: We identified that TRIM24 was coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2 weighted image abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, western blot, and immunohistochemistry demonstrated that TRIM24 activated the expression of the pluripotency transcription factor sex determining region Y-box 2 (Sox2) to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and Sox2 was validated by testing samples enrolled in our study and exploring external databases. CONCLUSIONS: Our findings uncover essential roles of the TRIM24-Sox2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management.

Brain tumors: Cancer stem-like cells interact with tumor microenvironment.

Cancer stem-like cells (CSCs) with potential of self-renewal drive tumorigenesis. Brain tumor microenvironment (TME) has been identified as a critical regulator of malignancy progression. Many researchers are searching new ways to characterize tumors with the goal of predicting how they respond to treatment. Here, we describe the striking parallels between normal stem cells and CSCs. We review the microenvironmental aspects of brain tumors, in particular composition and vital roles of immune cells infiltrating glioma and medulloblastoma. By highlighting that CSCs cooperate with TME via various cellular communication approaches, we discuss the recent advances in therapeutic strategies targeting the components of TME. Identification of the complex and interconnected factors can facilitate the development of promising treatments for these deadly malignancies.

Microsurgical treatment of craniopharyngioma: Experiences on 183 consecutive patients.

This study aimed to summarize the clinical experiences and postoperative effects of microsurgical approaches for craniopharyngioma.A total of 183 craniopharyngioma patients who underwent microsurgical treatment since March 2009 to March 2015 in our hospital were included in current research. Surgical approaches were selected based on preoperative evaluations, including tumor locations, sizes, and growth patterns. Active measurements to manage water-electrolyte disorder and insipidus were taken for postoperative treatments. During the follow-up, patients were monitored for residual or recurrent tumor by postoperative contrast MRI scans done 1 to 3 months after surgery.The used surgical approaches were as follows: frontopterional approach (76 cases), anterior interhemispheric approach (58 cases), transcallosal approach (10 cases), transsphenoidal approach (15 cases), unilateral subfrontal approach (15 cases), and combined approaches (9 cases). Around 124 cases (72.7%) received total tumor resection, 37 patients (20.2%) underwent subtotal resection, and 13 patients (7.1%) underwent partial removal. No significant difference was found on the postoperative complications among the different microsurgical approaches (all, P > .05). A total of 111 cases had an intact pituitary stalk preservation and 26 cases had partially preserved stalks during surgery. Visual improvement was achieved in 54 patients and visual deterioration occurred in 22 cases. Postoperative insipidus appeared in 114 cases and water-electrolyte disorder occurred in 99 cases. The postsurgical follow-up ranged from 3 to 69 months with a mean duration of 27.3 months and 23 patients suffered recurrence.Based on careful preoperative evaluation, microsurgical treatments may be safe and effective approach to improve postoperative outcomes of craniopharyngioma patients.

Anterior interhemispheric approach for removing large sellar region tumor.

The aim of the study was to explore anterior interhemispheric approach microsurgery for removing large sellar region tumors.A total of 118 patients with large sellar region tumors were treated with the anterior interhemispheric approach microsurgery. There were 58 craniopharyngioma, 37 pituitary adenoma, 5 hypothalamic glioma, 7 meningioma, and 11 other tumors cases. The maximal tumor diameter ranged from 3.0 to 8.2 cm, with a mean diameter of 4.3 cm. Diabetes insipidus and fluid and electrolyte imbalance were timely controlled after surgery. Postoperative examination of endocrine and of magnetic resonance imaging (MRI) enhancement scanning of the head were performed.Total, subtotal, and partial removal of tumors was, respectively, achieved in 80, 23, and 15 cases. A total of 109 patients had improved vision after surgery. During the hospital stay, 81 had diabetes insipidus, 68 had fluid and electrolyte imbalance, and 9 had hemorrhage and tumidness in the right frontal lobe (3 had frontal lobe contusion, and 6 had frontal lobe hematoma). The postoperative follow-up visit lasted for 3 to 105 months. During the follow-up period, 14 patients had recurrence of tumors, 38 cases had their single or multiple pituitary axis treated with hormonal replacement therapy for a long time after surgery, and 23 cases had to orally take drugs for the purpose of controlling diabetes insipidus.The anterior interhemispheric approach microsurgery is feasible for removing large sellar region tumors without significant sequels. Active postoperative managements of diabetes insipidus and fluid and electrolyte imbalance may help patients with earlier recovery.

Minimally invasive image-guided keyhole aspiration of cerebral abscesses.

Despite the low incidence of brain abscesses in Western nations (1-2%), the incidence in developing countries is as high as 8%. We evaluate a minimally invasive image-guided keyhole aspiration of cerebral abscesses and compare it with a series of cases treated with surgical excision. 23 patients (20 male and 3 female, aged 7-67 years) underwent image-guided burr hole aspiration of single or multiple cerebral abscesses. Patient characteristics, perioperative, and postoperative data were analyzed and compared with a second group of 22 patients (14 male and 8 female, aged 12-72) treated for cerebral abscesses with open surgical excision. In all cases, the surgical procedure was performed successfully without complication. 8 of the 23 aspiration cases were performed with the aid of iMRI. A comparison of patient demographics, duration of hospital stay, duration of antibiotic therapy, postoperative neurological recovery time, intraoperative blood loss, operative duration, length of incision, postoperative fever, repeat surgery, and mortality was performed between the aspiration and excision groups. Intraoperative blood loss, operative duration, length of incision, and postoperative fever were all significantly reduced in the aspiration group. Though, duration of hospital stay and antibiotic therapy and postoperative neurological recovery time were all increased in the aspiration group, and statistical significance was observed in all except the duration of hospital stay. This technique is a feasible and comparable minimally invasive alternative to open surgical excision and may provide reduced intraoperative blood loss, shortened operative duration, improved cosmetic outcomes, and a lessened incidence of postoperative fever.

[Trans-extradural approach to resect trigeminal schwannomas involving the cavernous sinus region].

OBJECTIVE: To investigate the techniques and effect of extradural approach for the resection of trigeminal schwannomas involving the cavernous sinus. METHODS: Twenty-three patients (range 26-63 years, mean age 46.2 years) with trigeminal schwannomas involving the cavernous sinus treated by middle fossa extradural approach were retrospectively analyzed. Frontotemporal orbitozygomatic extradural approach was performed in 2 patients. Frontotemporal zygomatic extradural approach was carried out in 21 patients. The first follow-up visit was on the 3rd month after surgery, and if residual was observed on enhanced MRI, then the patient was followed up every 6 months; otherwise, the patient was followed up every 8-12 months. RESULTS: The length of hospital stay after surgery was 7-13 days (mean 8.5 days). Two tumors originated from the ophthalmic branch, 2 from the maxillary branch, 5 from the mandibular branch and 14 from the gasserian ganglion. Total resection was achieved in 21 of the 23 patients (91.3%) and subtotal resection in the other 2 patients. All the patients were followed up from 3 months to 4 years. Median follow-up time was 19 months. The most common symptom was facial hypoesthesia, occurring in 18 patients. This symptom improved in 10 patients and worsened in 8 patients after surgery. New postoperative facial hypoesthesia was observed in 2 patients. Facial pain was observed in 3 patients and subsided after surgery. Two patients had loss of hearing, this symptom improved in 1 patient and worsened in 1 patient after surgery. Diplopia was observed in 6 patients. In 1 of these 6 patients, diplopia resulted from palsy of the oculomotor nerve. In the other 5 patients, diplopia resulted from palsy of the abducens nerve. This symptom improved postoperatively in all these 6 patients. New postoperative atrophy of the temporalis muscle was observed in 3 patients. There was no operation-related mortality. Tumor recurrence was only found in 1 patient after 24 months and was treated by Gamma knife. CONCLUSIONS: The middle fossa extradural approach may be an ideal option for the resection of trigeminal schwannomas involving the cavernous sinus. This approach produces no further impairment, less complication, and is less likely to injured the trigeminal nerve, abducens nerve, trochlear nerve and internal carotid artery.