ABSTRACT
Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a recently identified syndrome characterized by psychosis and dysautonomia. Treatment includes resection of the underlying tumor. While the pathologic mechanism involves disruption of NMDA function by anti-NMDA receptor autoantibodies, there are few descriptions of the perioperative management or anesthetic approach for such patients. We report a classic presentation of anti-NMDA receptor encephalitis and describe the use of total IV anesthesia with NMDA receptor-sparing drugs. Modest postoperative analgesic requirements, not reported in prior cases, are also described in our report.
ABSTRACT
Through digital karyotyping of permanent medulloblastoma cell lines, we found that the homeobox gene OTX2 was amplified more than 10-fold in three cell lines. Gene expression analyses showed that OTX2 transcripts were present at high levels in 14 of 15 (93%) medulloblastomas with anaplastic histopathologic features. Knockdown of OTX2 expression by siRNAs inhibited medulloblastoma cell growth in vitro, whereas pharmacologic doses of all-trans retinoic acid repressed OTX2 expression and induced apoptosis only in medulloblastoma cell lines that expressed OTX2. These observations suggest that OTX2 is essential for the pathogenesis of anaplastic medulloblastomas and that these tumors may be amenable to therapy with all-trans-retinoic acid.
Subject(s)
Antineoplastic Agents/pharmacology , Brain Neoplasms/genetics , Homeodomain Proteins/genetics , Medulloblastoma/drug therapy , Medulloblastoma/genetics , Nerve Tissue Proteins/genetics , Trans-Activators/genetics , Tretinoin/pharmacology , Brain Neoplasms/metabolism , Cell Growth Processes/drug effects , Cell Growth Processes/genetics , Cell Line, Tumor , Gene Amplification , Homeodomain Proteins/antagonists & inhibitors , Homeodomain Proteins/biosynthesis , Humans , Medulloblastoma/metabolism , Medulloblastoma/pathology , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/biosynthesis , Oncogenes/drug effects , Oncogenes/genetics , Otx Transcription Factors , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Trans-Activators/antagonists & inhibitors , Trans-Activators/biosynthesisABSTRACT
The phosphatidylinositol 3'-kinase pathway is activated in multiple advanced cancers, including glioblastomas, through inactivation of the PTEN tumor suppressor gene. Recently, mutations in PIK3CA, a member of the family of phosphatidylinositol 3'-kinase catalytic subunits, were identified in a significant fraction (25-30%) of colorectal cancers, gastric cancers, and glioblastomas and in a smaller fraction of breast and lung cancers. These mutations were found to cluster into two major "hot spots" located in the helical and catalytic domains. To determine whether PIK3CA is genetically altered in brain tumors, we performed a large-scale mutational analysis of the helical and catalytic domains. A total of 13 mutations of PIK3CA within these specific domains were identified in anaplastic oligodendrogliomas, anaplastic astrocytomas, glioblastoma multiforme, and medulloblastomas, whereas no mutations were identified in ependymomas or low-grade astrocytomas. These observations implicate PIK3CA as an oncogene in a wider spectrum of adult and pediatric brain tumors and suggest that PIK3CA may be a useful diagnostic marker or a therapeutic target in these cancers.