Neurofibromatosis Type 2 (NF2) and the Implications for Vestibular Schwannoma and Meningioma Pathogenesis.

Patients diagnosed with neurofibromatosis type 2 (NF2) are extremely likely to develop meningiomas, in addition to vestibular schwannomas. Meningiomas are a common primary brain tumor; many NF2 patients suffer from multiple meningiomas. In NF2, patients have mutations in the NF2 gene, specifically with loss of function in a tumor-suppressor protein that has a number of synonymous names, including: Merlin, Neurofibromin 2, and schwannomin. Merlin is a 70 kDa protein that has 10 different isoforms. The Hippo Tumor Suppressor pathway is regulated upstream by Merlin. This pathway is critical in regulating cell proliferation and apoptosis, characteristics that are important for tumor progression. Mutations of the NF2 gene are strongly associated with NF2 diagnosis, leading to benign proliferative conditions such as vestibular schwannomas and meningiomas. Unfortunately, even though these tumors are benign, they are associated with significant morbidity and the potential for early mortality. In this review, we aim to encompass meningiomas and vestibular schwannomas as they pertain to NF2 by assessing molecular genetics, common tumor types, and tumor pathogenesis.

COVID-19 Vaccine Mandates for Healthcare Professionals in the United States.

Healthcare workers (HCWs) need to be vaccinated against COVID-19 because they care for vulnerable patients. Hesitation to receiving the COVID-19 vaccine stems from the argument of bodily autonomy, novel mRNA vaccine technology, and conspiracy theories. However, vaccinations may prevent thousands of hospitalizations and deaths. HCWs have previously complied with other required vaccinations to care for children, elderly, and immunocompromised patients. Yet, COVID-19 vaccination mandates in the healthcare setting have been faced with resistance and subsequent staffing shortages. As HCWs display their hesitation to the vaccine, the community loses trust in its efficacy and safety. Speculation on pharmaceutical profiteering has also contributed to vaccine mistrust. As the pandemic continues, the healthcare field must decide on a course of action: adhere to vaccination mandates and cope with decreased staffing, repeal vaccination mandates to recover staff, rely on personal protective equipment (PPE) alone for protection, or do nothing and expect survival through herd immunity. To date, the United States has chosen to mandate COVID-19 vaccinations for any healthcare worker employed by Medicare and/or Medicaid-accepting facilities, allowing allergy and religious exemptions. This COVID-19 vaccination mandate for HCWs ethically protects the vulnerable people who HCWs vow to care for.

A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient.

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient's platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Advances in Immunotherapy for the Treatment of Adult Glioblastoma: Overcoming Chemical and Physical Barriers.

Glioblastoma, or glioblastoma multiforme (GBM, WHO Grade IV), is a highly aggressive adult glioma. Despite extensive efforts to improve treatment, the current standard-of-care (SOC) regimen, which consists of maximal resection, radiotherapy, and temozolomide (TMZ), achieves only a 12-15 month survival. The clinical improvements achieved through immunotherapy in several extracranial solid tumors, including non-small-cell lung cancer, melanoma, and non-Hodgkin lymphoma, inspired investigations to pursue various immunotherapeutic interventions in adult glioblastoma patients. Despite some encouraging reports from preclinical and early-stage clinical trials, none of the tested agents have been convincing in Phase III clinical trials. One, but not the only, factor that is accountable for the slow progress is the blood-brain barrier, which prevents most antitumor drugs from reaching the target in appreciable amounts. Herein, we review the current state of immunotherapy in glioblastoma and discuss the significant challenges that prevent advancement. We also provide thoughts on steps that may be taken to remediate these challenges, including the application of ultrasound technologies.

Pearls & Oy-sters: Pivoting Treatment Regimens of Pediatric Atypical Teratoid Rhabdoid Tumors to Optimize Care in Adult ATRT: A Case Report.

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant embryonal tumor of the CNS, largely affecting pediatric patients, with exceedingly rare cases in adults at an estimated annual incidence of 1/1,000,000. We report a unique case of ATRT in a 43-year-old female patient who first presented with progressive focal headaches. Imaging revealed a sellar mass with suprasellar extensions, which was partially removed via a transsphenoidal resection. The tumor aggressively recurred just 1 month postoperatively. Her care team pursued a novel treatment plan by using a slightly modified COG ACNS 0332 regimen, which involved radiation, followed by 4 cycles of monthly chemotherapy including vincristine, cyclophosphamide, and cisplatin. Hematopoietic stem cells were collected between radiation and chemotherapy in the event that the patient required stem cell salvage therapy postadjuvant chemotherapy. The MRIs taken at 2 and 4 months postrecurrence indicated a substantial decrease in tumor volume, with corresponding clinical improvements to cranial nerve deficits. Given the scarcity of literature on adult cases of ATRT and the lack of a standard of care for these cases, discussing the efficacy of our patient's treatment plan may aid clinical decision making for adult ATRT cases.

Therapeutically leveraging GABAA receptors in cancer.

γ-aminobutyric acid or GABA is an amino acid that functionally acts as a neurotransmitter and is critical to neurotransmission. GABA is also a metabolite in the Krebs cycle. It is therefore unsurprising that GABA and its receptors are also present outside of the central nervous system, including in immune cells. This observation suggests that GABAergic signaling impacts events beyond brain function and possibly human health beyond neurological disorders. Indeed, GABA receptor subunits are expressed in pathological disease states, including in disparate cancers. The role that GABA and its receptors may play in cancer development and progression remains unclear. If, however, those cancers have functional GABA receptors that participate in GABAergic signaling, it raises an important question whether these signaling pathways might be targetable for therapeutic benefit. Herein we summarize the effects of modulating Type-A GABA receptor signaling in various cancers and highlight how Type-A GABA receptors could emerge as a novel therapeutic target in cancer.

Reuse of Molecules for Glioblastoma Therapy.

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12-18 months. New and emerging treatments include the application of a physical device, non-invasive 'tumor treating fields' (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use.