Gonadal sex patterns p21-induced cellular senescence in mouse and human glioblastoma.

Males exhibit higher incidence and worse prognosis for the majority of cancers, including glioblastoma (GBM). Disparate survival may be related to sex-biased responses to treatment, including radiation. Using a mouse model of GBM, we show that female cells are more sensitive to radiation, and that senescence represents a major component of the radiation therapeutic response in both sexes. Correlation analyses revealed that the CDK inhibitor p21 and irradiation induced senescence were differentially regulated between male and female cells. Indeed, female cellular senescence was more sensitive to changes in p21 levels, a finding that was observed in wildtype and transformed murine astrocytes, as well as patient-derived GBM cell lines. Using a novel Four Core Genotypes model of GBM, we further show that sex differences in p21-induced senescence are patterned during early development by gonadal sex. These data provide a rationale for the further study of sex differences in radiation response and how senescence might be enhanced for radiation sensitization. The determination that p21 and gonadal sex are required for sex differences in radiation response will serve as a foundation for these future mechanistic studies.

Progeny in an Inhospitable Milieu-Solitary Intraventricular Metastasis From a Triple-Negative Breast Cancer Mimicking Central Neurocytoma: Case Report and Review of Diagnostic Pitfalls and Management Strategies.

BACKGROUND: Triple-negative breast cancer (TNBC) is one of the most invasive subtypes of breast cancer, with high rates of visceral metastases and recurrence. Choroid plexus metastasis from breast cancer is infrequent despite a high incidence of brain parenchymal metastasis. METHODS: We report a case of solitary metastasis to the choroid plexus from a TNBC that masqueraded as central neurocytoma, and we review the PubMed database for similar cases focusing on their diagnostic challenges and management strategies. RESULTS: A 28-year-old woman with a history of TNBC presented with recurrent seizures, headache, and vomiting. Imaging studies depicted a well-defined lesion in the right anterior lateral ventricle that was attached to the septum pellucidum. After an initial radiological diagnosis of central neurocytoma, she deteriorated rapidly with intraventricular hemorrhage requiring emergency transcallosal microsurgical tumor decompression. Histopathological examination and immunohistochemistry confirmed breast carcinoma as the origin of the intraventricular mass. A review of the PubMed database identified only 2 case reports of choroid plexus metastases from breast cancer reported thus far. CONCLUSIONS: Choroid plexus metastases are exceedingly infrequent and can be mistaken for the more common central neurocytoma. The intraventricular milieu is inhospitable suggesting some extracranial carcinomas develop traits that help them to thrive in the acellular cerebrospinal fluid. Intraventricular mass lesions with a history of primary neoplasm should raise suspicion for choroid plexus metastases. A high index of suspicion despite excellent control of the primary tumor and the absence of systemic metastases is indispensable.