RUNX1 and RUNX2 transcription factors function in opposing roles to regulate breast cancer stem cells.

Breast cancer stem cells (BCSCs) are competent to initiate tumor formation and growth and refractory to conventional therapies. Consequently BCSCs are implicated in tumor recurrence. Many signaling cascades associated with BCSCs are critical for epithelial-to-mesenchymal transition (EMT). We developed a model system to mechanistically examine BCSCs in basal-like breast cancer using MCF10AT1 FACS sorted for CD24 (negative/low in BCSCs) and CD44 (positive/high in BCSCs). Ingenuity Pathway Analysis comparing RNA-seq on the CD24-/low versus CD24+/high MCF10AT1 indicates that the top activated upstream regulators include TWIST1, TGFß1, OCT4, and other factors known to be increased in BCSCs and during EMT. The top inhibited upstream regulators include ESR1, TP63, and FAS. Consistent with our results, many genes previously demonstrated to be regulated by RUNX factors are altered in BCSCs. The RUNX2 interaction network is the top significant pathway altered between CD24-/low and CD24+/high MCF10AT1. RUNX1 is higher in expression at the RNA level than RUNX2. RUNX3 is not expressed. While, human-specific quantitative polymerase chain reaction primers demonstrate that RUNX1 and CDH1 decrease in human MCF10CA1a cells that have grown tumors within the murine mammary fat pad microenvironment, RUNX2 and VIM increase. Treatment with an inhibitor of RUNX binding to CBFß for 5 days followed by a 7-day recovery period results in EMT suggesting that loss of RUNX1, rather than increase in RUNX2, is a driver of EMT in early stage breast cancer. Increased understanding of RUNX regulation on BCSCs and EMT will provide novel insight into therapeutic strategies to prevent recurrence.

Addition of clobazam successfully treating drug resistant seizures in Heidenhain variant Creutzfeldt Jakob disease: A case report.

Creutzfeldt Jakob Disease (CJD) is a rapidly progressive and fatal neurodegenerative disease that is uncommonly accompanied with seizures. In this case report, we describe a 63-year-old male patient who presented with a 3-week history of visual disturbances and clonic movement of his left arm. Additionally, the patient was reported to have developed erratic behaviors along with insomnia during this period. An EEG showed 4 electrographic seizures of bilateral temporo-occipital onset characterized by 1.5 Hz periodic discharges, lasting 2-13 min. Levetiracetam was started and titrated to the maximal dose however seizures continued so lacosamide and clonazepam were initiated. Despite these aggressive treatments, seizures continued, and oral clobazam 5 mg BID replaced clonazepam. Continued electrographic seizures warranted an increase in clobazam to 10 mg BID after which the seizures stopped; of note, lateralized periodic discharges (LPDs) remained. The patient's symptoms were consistent with the Heidenhain variant, along with probable CJD due to positive RT-QuIC assay, positive 14-3-3 protein, MRI FLAIR hyperintensities, and EEG findings. Although the patient passed away 3 weeks following admission as a result of CJD, we propose that there may be clinical benefit in the use of clobazam in suspected CJD patients presenting with seizures, and its use merits further investigation.

Pallidal stimulation-induced psychosis and suicidality in Parkinson's disease.

Neuropsychiatric adverse events have been previously reported following deep brain stimulation (DBS) for Parkinson's disease (PD). Most cases described have involved DBS of the subthalamic nucleus (STN). We report a unique case of acute-onset and reversible psychosis, suicidality, and depressive symptoms following DBS of the globus pallidus internus (GPi) and review the relevant literature.

Clinical Reasoning: A 67-Year-Old Woman With Abdominal Pain, Constipation, and Urinary Retention.

Meningeal melanocytomas are an extremely rare, pigmented tumors of the central nervous system (CNS). They generally carry a favorable prognosis, although recurrence and transformation into the more aggressive malignant melanoma has been reported. We present a case of a patient who reported constipation and abdominal pain around the umbilicus, which progressed into cord compression with lower extremity weakness and gait instability. Spinal magnetic resonance imaging (MRI) revealed a tumor at the level of T11, and she underwent gross total resection of the mass. Pathology demonstrated a meningeal melanocytoma with intermediate features. She received post-operative radiation therapy and had stable disease for three years, at which time she developed new weakness and drop metastases. This case represents a rare presentation of a rare disease, in which a spinal cord tumor presented with constipation and abdominal distress. Intradural-extramedullary tumors of the thoracic spine are most commonly nerve sheath tumors or meningiomas, but rare entities such as melanocytomas can present in this location; even more rarely, these tumors can have an aggressive course with delayed recurrence.