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Tumor surveillance is a common practice in oncology; its goal is timely detection of cancer progression, which is typically diagnosed by Visual Comparison (VC) or bidirectional measurement of longitudinal radiological images. Low-grade gliomas (LGG) can cause significant neurological morbidity by progressive brain invasion over time. We analyzed the longitudinal magnetic resonance imaging (MRI) studies of patients, diagnosed with grade 2 gliomas without any radiation therapy at the initial diagnosis, who had at least 4 MRI studies. Forty-eight patients met the inclusion criteria, including 13 oligodendrogliomas, 24 astrocytomas and 11 mixed gliomas. Thirty-four patients had clinical progression (CP) and 14 patients were considered clinically stable (CS) by VC at the time of the study. The computer assisted diagnosis (CAD) method consisted of segmentation of the fluid-attenuated inversion recovery (FLAIR) images, computing tumor volumes, and determining progression by the online abrupt change of point method, which considered only past MRIs. In the CP group, CAD detected progression at earlier times than the clinical diagnosis in 26/34 patients. In the CS group, CAD detected progression in 10/14 patients. Six physicians from the departments of neurology (neuro-oncology), radiology, and radiation oncology reviewed and agreed with the progression determined by the CAD method including the study subjects in the CS group. CAD was able to diagnose tumor progression when the tumor size grew at an average of 74% (range 14% to 364%) since the base line compared to 320% (range 25% to 2019%) in the VC method. The average time to progression was only 17 months when CAD was used compared to 50 months when VC method was used. Early detection of tumor progression is critical for LGG patients because it can optimize therapeutic options with significantly lower volume of brain resection or irradiation

Background Glioblastoma (GBM) is the most common malignant brain tumor, and glioma stem cells (GSCs) are considered a major source of treatment resistance for glioblastoma. Identifying new compounds that inhibit the growth of GSCs and understanding their underlying molecular mechanisms are therefore important for developing novel therapy for GBM. Methods We investigated the potential inhibitory effect of isorhapontigenin (ISO), an anticancer compound identified in our recent investigations, on anchorage-independent growth of patient-derived glioblastoma spheres (PDGS) and its mechanism of action. Results ISO treatment resulted in significant anchorage-independent growth inhibition, accompanied with cell cycle G0-G1 arrest and cyclin D1 protein downregulation in PDGS. Further studies established that cyclin D1 was downregulated by ISO at transcription levels in a SOX2-dependent manner. In addition, ISO attenuated SOX2 expression by specific induction of miR-145, which in turn suppressed 3'UTR activity of SOX2 mRNA without affecting its mRNA stability. Moreover, ectopic expression of exogenous SOX2 rendered D456 cells resistant to induction of cell cycle G0-G1 arrest and anchorage-independent growth inhibition upon ISO treatment, whereas inhibition of miR-145 resulted in D456 cells resistant to ISO inhibition of SOX2 and cyclin D1 expression. In addition, overexpression of miR-145 mimicked ISO treatment in D456 cells. Conclusions ISO induces miR-145 expression, which binds to the SOX2 mRNA 3'UTR region and inhibits SOX2 protein translation. Inhibition of SOX2 leads to cyclin D1 downregulation and PDGS anchorage-independent growth inhibition. The elucidation of the miR-145/SOX2/cyclin D1 axis in PDGS provides a significant insight into understanding the anti-GBM effect of ISO compound.

Background Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Methods Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. Results We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Conclusions Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted.