Search

Glioblastoma continues to rank among the most lethal primary human tumors. Despite treatment with the most rigorous surgical, chemotherapeutic, and radiation regimens, the median survival is just 12-15 months after diagnosis for patients with glioblastoma. One feature of glioblastoma associated with poor prognosis is the degree of hypoxia and expression levels of hypoxia-inducible factor-1 α (HIF-1α). HIF-1α expression allows metabolic adaptation to low oxygen availability, partly through upregulation of vascular endothelial growth factor (VEGF) and increased tumor angiogenesis. In this study, we demonstrate an induced level of astrocyte-elevated gene-1 (AEG-1) in high-grade as compared to low-grade astrocytomas and association of AEG-1 with necrotic areas in glioblastoma. AEG-1 was recently demonstrated to be an oncogene that can induce angiogenesis in glioblastoma. Results from in vitro studies show that AEG-1 is induced by hypoxia in a HIF-1α-dependent manner and that PI3K inhibition abrogates AEG-1 induction during hypoxia. Furthermore, we show that AEG-1 is induced by glucose deprivation and that prevention of intracellular reactive oxygen species (ROS) accumulation prevents this induction. Additionally, AEG-1 knockdown results in increased, whereas AEG-1 overexpression results in decreased, ROS production and glucose deprivation-induced cytotoxicity, indicating that AEG-1 induction is necessary for cells to survive this type of stress. Moreover, AEG-1 modulates the expression of glycolytic enzymes in glioblastoma cells in vitro and in vivo and regulates the expression of these enzymes as well as glycolytic flux during metabolic stress, such as glucose deprivation. The AEG-1-induced glycolytic profile in glioblastoma cells is also modulated by glycolytic inhibition. Studies in nude mice demonstrate that AEG-1 knockdown reduces the growth of glioblastoma xenografts and also promotes chemosensitivity to glycolytic inhibition in vitro. These findings identify a novel role for AEG-1 in the regulation of glycolysis in glioblastoma and indicate that anti-glycolytic therapies may be useful in treating malignancies that demonstrate AEG-1-overexpression.

Introduction: Our previous studies have demonstrated that tumor-infiltrating lymphocytes (TILs), including normal B cells, T cells, and natural killer (NK) cells, in diffuse large B-cell lymphoma (DLBCL) have a significantly favorable impact on the clinical outcomes of patients treated with standard chemoimmunotherapy. In this study, to gain a full overview of the tumor immune microenvironment (TIME), we assembled a flow cytometry cohort of 102 patients diagnosed with DLBCL at the Duke University Medical Center. Methods: We collected diagnostic flow cytometry data, including the proportion of T cells, abnormal B cells, normal B cells, plasma cells, NK cells, monocytes, and granulocytes in fresh biopsy tissues at clinical presentation, and analyzed the correlations with patient survival and between different cell populations. Results: We found that low T cell percentages in all viable cells and low ratios of T cells to abnormal B cells correlated with significantly poorer survival, whereas higher percentages of normal B cells among total B cells (or high ratios of normal B cells to abnormal B cells) and high percentages of NK cells among all viable cells correlated with significantly better survival in patients with DLBCL. After excluding a small number of patientswith low T cell percentages, the normal B cell percentage among all B cells, but not T cell percentage among all cells, continued to show a remarkable prognostic effect. Data showed significant positive correlations between T cells and normal B cells, and between granulocytes and monocytes. Furthermore, we constructed a prognostic model based on clinical and flow cytometry factors, which divided the DLBCL cohort into two equal groups with remarkable differences in patient survival and treatment response. Summary: TILs, including normal B cells, T cells, and NK cells, are associated with favorable clinical outcomes in DLBCL, and flow cytometry capable of quantifying the TIME may have additional clinical utility for prognostication. [ABSTRACT FROM AUTHOR]

The 2021 "World Health Organization (WHO) Classification of Thoracic Tumours" classifies epithelial tumors of the thymus (thymomas) based on cytomorphology. Thymomas with benign cytomorphology are classified as type A, AB, B1, B2, and B3, while those with malignant cytomorphology are classified as thymic carcinoma. Although all thymomas have malignant potential, extra-thoracic metastasis of thymomas is exceedingly rare and the exact incidence is not known. Literature review demonstrated 39 cases of thymoma with extra-thoracic metastases reported since the publication of the 1999 WHO Classification of Thoracic Tumours. Nine of these cases presented with metastasis to the liver in the setting of concurrent metastasis to other organs, while only three cases metastasized solely to the liver. We herein report a well-documented case of type B1 thymoma with relatively limited stage (IIb) with an isolated, single liver metastasis occurring seven years after primary resection in a patient with concomitant myasthenia gravis. The following report includes a review of the literature, a discussion of thymoma classification and its relevance to prognosis, and an overview of other extra-thoracic metastatic thymoma cases. [ABSTRACT FROM AUTHOR]