Benign and malignant tumors of the central nervous system and pregnancy.

Tumors of the central nervous system (CNS) are rare entities, typically affecting the very young or the very old, but span a spectrum of disease that may present in any age group. Women of reproductive age are more likely to be affected by benign tumors, including pituitary adenomas and meningiomas, and aggressive intracranial malignancies, such as brain metastases and glioblastoma, rarely present in pregnancy. Definitive management of CNS tumors may involve multimodal therapy, including surgery, radiation, and chemotherapy, and each of these treatments carries risk to the mother and developing fetus. CNS tumors often present with challenging and morbid symptoms such as headache and seizure, which need to be managed throughout a pregnancy. Decisions about timing treatment during pregnancy or delaying until after delivery, continuing or electively terminating a pregnancy, and future family planning and fertility are complex and require a multidisciplinary care team to evaluate the implications to both mother and baby. There are no guidelines or consensus recommendations regarding brain tumor management in pregnancy, and thus, individual treatment decisions are made by the care team based on experiential evidence, extrapolation of guidelines for nonpregnant patients, and patient values and preferences.

Threonyl-tRNA synthetase overexpression correlates with angiogenic markers and progression of human ovarian cancer.

BACKGROUND: Ovarian tumors create a dynamic microenvironment that promotes angiogenesis and reduces immune responses. Our research has revealed that threonyl-tRNA synthetase (TARS) has an extracellular angiogenic activity separate from its function in protein synthesis. The objective of this study was to test the hypothesis that TARS expression in clinical samples correlates with angiogenic markers and ovarian cancer progression. METHODS: Protein and mRNA databases were explored to correlate TARS expression with ovarian cancer. Serial sections of paraffin embedded ovarian tissues from 70 patients diagnosed with epithelial ovarian cancer and 12 control patients were assessed for expression of TARS, vascular endothelial growth factor (VEGF) and PECAM using immunohistochemistry. TARS secretion from SK-OV-3 human ovarian cancer cells was measured. Serum samples from 31 tissue-matched patients were analyzed by ELISA for TARS, CA-125, and tumor necrosis factor-α (TNF-α). RESULTS: There was a strong association between the tumor expression of TARS and advancing stage of epithelial ovarian cancer (p < 0.001). TARS expression and localization were also correlated with VEGF (p < 0.001). A significant proportion of samples included heavy TARS staining of infiltrating leukocytes which also correlated with stage (p = 0.017). TARS was secreted by ovarian cancer cells, and patient serum TARS was related to tumor TARS and angiogenic markers, but did not achieve significance with respect to stage. Multivariate Cox proportional hazard models revealed a surprising inverse relationship between TARS expression and mortality risk in late stage disease (p = 0.062). CONCLUSIONS: TARS expression is increased in epithelial ovarian cancer and correlates with markers of angiogenic progression. These findings and the association of TARS with disease survival provide clinical validation that TARS is associated with angiogenesis in ovarian cancer. These results encourage further study of TARS as a regulator of the tumor microenvironment and possible target for diagnosis and/or treatment in ovarian cancer.