MicroRNA-92b targets tumor suppressor gene FBXW7 in glioblastoma

IntroductionGlioblastoma (GBM) is a highly aggressive and lethal primary brain tumor. Despite limited treatment options, the overall survival of GBM patients has shown minimal improvement over the past two decades. Factors such as delayed cancer diagnosis, tumor heterogeneity, cancer stem cell survival, infiltrative nature of GBM cells, metabolic reprogramming, and development of therapy resistance contribute to treatment failure. To address these challenges, multitargeted therapies are urgently needed for improved GBM treatment outcomes. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Dysregulated miRNAs have been identified in GBM, playing roles in tumor initiation, progression, and maintenance. Among these miRNAs, miR-92b (miRNA-92b-3p) has been found to be overexpressed in various cancers, including GBM. However, the specific target genes of miR-92b and its therapeutic potential in GBM remain poorly explored.MethodsSamples encompassed T98G, U87, and A172 human GBM cell lines, GBM tumors from Puerto Rican patients, and murine tumors. In-situ hybridization (ISH) assessed miR-92b expression in patient tumors. Transient and stable transfections modified miR-92b levels in GBM cell lines. Real-time PCR gauged gene expressions. Caspase 3 and Trypan Blue assays evaluated apoptosis and viability. Bioinformatics tools (TargetScanHuman 8.0, miRDB, Diana tools, miRWalk) predicted targets. Luciferase assays and Western Blots validated miRNA-target interactions. A subcutaneous GBM Xenograft mouse model received intraperitoneal NC-OMIs or miR92b-OMIs encapsulated in liposomes, three-times per week for two weeks. Analysis utilized GraphPad Prism 8; statistical significance was assessed using 2-tailed, unpaired Student’s t-test and two-way ANOVA as required.ResultsThis study investigated the expression of miR-92b in GBM tumors compared to normal brain tissue samples, revealing a significant upregulation. Inhibition of miR-92b using oligonucleotide microRNA inhibitors (OMIs) suppressed GBM cell growth, migration, and induced apoptosis, while ectopic expression of miR-92b yielded opposite effects. Systemic administration of liposomal-miR92b-OMIs in GBM xenograft mice resulted in reductions in tumor volume and weight. Subsequent experiments identified F-Box and WD Repeat Domain Containing 7 (FBXW7) as a direct target gene of miR-92b in GBM cells.DiscussionFBXW7 acts as a tumor suppressor gene in various cancer types, and analysis of patient data demonstrated that GBM patients with higher FBXW7 mRNA levels had significantly better overall survival compared to those with lower levels. Taken together, our findings suggest that the dysregulated expression of miR-92b in GBM contributes to tumor progression by targeting FBXW7. These results highlight the potential of miR-92b as a therapeutic target for GBM. Further exploration and development of miR-92b-targeted therapies may offer a novel approach to improve treatment outcomes in GBM patients

Ventriculoperitoneal shunt knotting causing bowel obstruction and necrosis in an adult patient.

Knotting or twisting of the peritoneal catheter around a bowel segment, causing bowel obstruction and necrosis, is extremely rare. Only six cases have been reported in the literature. This report described the second case of an adult patient with spontaneous knotting of the peritoneal catheter around a small-bowel segment, causing bowel obstruction and necrosis. The presentation of a knotted ventriculoperitoneal shunt around a bowel loop is stereotypical. Treatment and general recommendations have been made to help guide clinicians when encountering such cases. Evidence of small-bowel obstruction in a twisted, coiled or knotted peritoneal catheter may need surgical intervention. In the setting of progressive abdominal manifestations, knotting of the peritoneal catheter around bowel loops may cause bowel obstruction and may present with acute life-threatening manifestations. Efficient and expedite diagnosis should be made to coordinate multispecialty intervention and follow-up appropriately

Single-stage cranioplasty with customized polyetheretherketone implant after tumor resection using virtual reality and augmented reality for precise implant customization and placement: illustrative case.

BACKGROUND: Cranioplasties are routinely performed to restore cosmesis and to protect intracranial contents after trauma, resection of tumors, or other pathologies. Traditionally done as a second-stage procedure, new single-stage cranioplasty protocols have been developed to minimize recovery periods, decrease complications, and improve patient satisfaction. These protocols, however, still require the use of larger than planned implants or use larger than ideal incisions to accommodate three-dimensional (3D) templates, which may not be optimal in regions with complex bony anatomy. OBSERVATIONS: A 50-year-old woman with a painful and progressively enlarging hemangioma of the left frontal bone underwent a single-stage resection followed by custom cranioplasty using a new extended reality (XR)-based workflow. Excellent cosmetic results, decreased operative time, and a feasible workflow were achieved. LESSONS: The use of an XR-based visualization platform allows the surgeon to treat lesions and perform custom cranioplasties in one session while avoiding common pitfalls of current single-stage workflows, such as increased operative times for tailoring implants, as well as minimizing the use of 3D overlay models, which may not appropriately conform to complex regional bony anatomy intraoperatively

Middle cerebellar peduncle approach for Nocardia brainstem abscess: illustrative case.

BACKGROUND: Nocardia cyriacigeorgica represents a rare cause of cerebral abscesses. Rarer still are brainstem abscesses caused by this bacterial species in immunocompetent hosts. In fact, only one such brainstem abscess case has been described in the neurosurgical literature to our knowledge to date. Herein, a case of Nocardia cyriacigeorgica abscess in the pons is reported, as well as a description of its surgical evacuation via the transpetrosal fissure, middle cerebellar peduncle approach. The authors review the utility of this well-described approach in treating such lesions safely and effectively. Finally, the authors briefly review, compare, and contrast related cases to this one. OBSERVATIONS: Augmented reality is additive to and useful for well-described safe entry corridors to the brainstem. Despite surgical success, patients may not regain previously lost neurological function. LESSONS: The transpetrosal fissure, middle cerebellar peduncle approach is safe and effective in evacuating pontine abscesses. Augmented reality guidance supplements but does not replace thorough knowledge of operative anatomy for this complex procedure. A reasonable degree of suspicion for brainstem abscess is prudent even in immunocompetent hosts. A multidisciplinary team is critical to the successful treatment of central nervous system Nocardiosis

Primary diffuse large B cell lymphoma of the optic chiasm in an immunocompetent patient.

Primary lymphoma of the visual pathway is rare, especially at the chiasm. Very few cases have been reported. The lesion is frequently confused with an optic-hypothalamic glioma. A 55-year-old man was found disoriented at his home by a friend and evaluated with a brain MRI which demonstrated an expansile mass located at the optic chiasm and hypothalamus level. The principal differential was a high-grade hypothalamic glioma due to the contrast enhancement. A biopsy of the chiasmal lesion was performed. Histological diagnosis of the lesion was compatible with a diffuse large B cell lymphoma. He was started on methotrexate and rituximab; however, his clinical course kept deteriorating, and he died 64 days after his presentation. All prior cases of primary lymphoma of the chiasm are reviewed

Huge subcutaneous extraperitoneal pseudocyst after migration of the ventriculoperitoneal shunt catheter.

The formation of an intraperitoneal pseudocyst as a complication of ventriculoperitoneal shunts is well known. However, the formation of a pseudocyst at the subcutaneous extraperitoneal abdominal space is unusual and likely secondary to the migration of the peritoneal catheter. We present a 53-year-old male who had placement of a ventriculoperitoneal shunt for hydrocephalus secondary to a vestibular schwannoma. Five months later, he presented with an enormously distended abdomen. Investigations showed the peritoneal catheter in the extraperitoneal space within a large right lower quadrant abdominal wall pseudocyst. The patient was taken to the operating theatre, and the shunt was externalised at the original abdominal incision. Approximately 3 L of cerebrospinal fluid were aspirated from the distal peritoneal catheter. After negative cultures, a new peritoneal catheter was placed intraperitoneally at the contralateral lower abdominal quadrant. The contralateral quadrant was utilised to prevent fluid accumulation into the old extraperitoneal cavity

Feasibility of exoscopic keyhole surgery: case series.

Keyhole approaches, performed with the endoscope, microscope, or exoscope, aim to minimize tissue traumatization while maximizing surgical view. The exoscope can provide better ergonomics than the microscope without restricting the space inside of the keyhole, as when using the endoscope. However, a frequently quoted reason for intraoperative exoscope-to-microscope conversion is the absence of sufficient light. In this video, the authors present 4 patients who underwent posterior fossa keyhole surgery without intraoperative conversion. The surgical objective was achieved in all patients without associated morbidity. After adequate adaptation, the exoscope allows sufficient light in the surgical field to perform safe keyhole surgery. The video can be found here: https://stream.cadmore.media/r10.3171/2023.10.FOCVID23116