Genetic expression profiles of adult and pediatric ependymomas: molecular pathways, prognostic indicators, and therapeutic targets.

Ependymomas are tumors that can present within either the intracranial or spinal regions. While 90% of all pediatric ependymomas are intracranial, spinal cord ependymomas are more commonly found in patients 20-40 years old. Treatment for spinal lesions has achieved local control rates up to 100% following gross total resection, while pediatric intracranial tumors have 40-60% mortality. Given the inability to effectively treat ependymomas with current standard practices, researchers have focused their efforts on evaluating chromosomal alterations, genetic expression profiles, epigenetic events, and molecular pathways. While these studies have provided critical insight into the potential mechanisms underlying ependymoma pathogenesis, understanding of the intricate interplay between the various pathways involved in tumor initiation, development, and progression will require deeper investigation. However, several potential prognostic markers and therapeutic targets have been identified, providing key areas of focus for future research. The utilization of unique genetic expression profiles based upon patient age, tumor location, tumor grade, and subtype has revealed a multitude of findings warranting further study. Inspection of various molecular pathways associated with ependymomas may establish the foundation for developing novel therapies capable of achieving significant clinical improvements with individualized regimens specifically designed for personalized treatment strategies.

Chromosomal alterations, prognostic factors, and targeted molecular therapies for malignant meningiomas.

Meningiomas are the second most common intracranial neoplasm in adults and originate from arachnoidal cap cells. Malignant meningiomas are resistant to conventional treatments such as surgery, chemotherapy, and radiotherapy. Unlike benign meningiomas, atypical and anaplastic tumors generally display more complex karyotypes associated with aggressive behavior. While these chromosomal anomalies are associated with greater malignancy in meningiomas, the specific genes involved remain unknown. Malignant meningiomas are characterized by increased tumor aggressiveness, rapid recurrence, local invasion, atypical histological appearance, and a high mitotic index. Potential prognostic factors include extent of resection, treatment with radiotherapy or stereotactic radiosurgery, Ki-67/MIB-1 labeling index, p53 overexpression, percentage of tumor cells in the S-phase, telomerase activity, and numerous genetic expression profiles. A greater understanding of prognostic factors and molecular markers involved in critical signaling pathways may aid in the identification of novel therapeutic targets. As such, further studies are needed to establish reliable prognostic factors and develop more effective treatments for malignant meningiomas.

An analysis of intracranial epidermoid tumors with malignant transformation: treatment and outcomes.

OBJECTIVE: While typically benign, epidermoid tumors upon rare occasion can undergo malignant transformation, which carries a poor prognosis. Here, we reviewed treatment strategies and analyzed outcomes for every case of malignant epidermoid tumor reported since its original description in 1912. METHODS: A comprehensive literature review identified all reported cases of malignant transformation of intracranial epidermoid tumor. Treatments were categorized as follows: palliative management, stereotactic radiosurgery (SRS), chemotherapy, and surgery plus multiple (2+) adjuvant therapies. Survival data of these groups were compared to treatment outcomes for patients receiving only surgical resection, as reported in our previous study. RESULTS: We identified 58 cases of intracranial epidermoid tumor with malignant degeneration. Average survival regardless of therapy was 11.8 months. Mean survival outcomes for groups treated with palliative management, chemotherapy, SRS, and multiple postoperative adjuvant therapies were 5.3 months, 25.7 months, 29.2 months, and 36.3 months, respectively. Outcomes for the groups including SRS, chemotherapy, and multiple post-operative adjuvant therapies were statistically significant compared to surgical resection alone. CONCLUSION: While there remains a lack of consensus regarding the best approach to the management of patients with malignant epidermoid tumors, our systematic analysis characterizes and confirms the added benefit of SRS, chemotherapy, and multimodal adjuvant therapies.

Endogenous vaults and bioengineered vault nanoparticles for treatment of glioblastomas: implications for future targeted therapies.

Endogenous vaults are ribonucleoproteins expressed throughout various cell types and across numerous species. Several central nervous system (CNS) tumors have been reported to exhibit high levels of major vault protein (MVP). The vault has been hypothesized to play a role in cellular transport. Although further studies are needed to elucidate the mechanisms of endogenous vault function, these advances may enable the development of targeted therapies to prevent cancer cells from acquiring MVP-related drug resistance. In addition, they seem suited for use as nanocapsules for delivering various therapeutic agents and immunogenic proteins, representing a promising prospect for CNS tumor immunotherapy.

Passive immunotherapeutic strategies for the treatment of malignant gliomas.

This review provides historical and recent perspectives related to passive immunotherapy for high-grade gliomas. The authors discuss approaches that use lymphokine-activated killer cells, cytotoxic T lymphocytes, and monoclonal antibodies.