I: Serum tumor biomarker for Medulloblastomas
Medulloblastoma (MB) is one of the most malignant and frequent childhood brain tumors. Development of a non-invasive assay to detect MB in early stages might improve the life of many children. Accordingly, identification of circulating tumor biomarkers in MB patients would facilitate screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis for survival after clinical intervention. The transcription factor OTX2, which is normally silenced in the adult brain, is overexpressed in the majority of MBs (60-75%). In this study, we hypothesized that OTX2 mRNA encapsulated in extracellular vesicles (EVs) can serve as a non-invasive, early diagnostic and/or …show more content…
Overexpression of several pre-RC elements have been identified in different cancer types, including medulloblastoma (MB). Notably, overexpression of minichromosome maintenance (MCM) proteins 2, 3 and 7 is associated with migration and invasion in MB. In this study, we provide a more comprehensive mRNA expression profiling of a larger set of pre-RC elements in different MB cell lines and tumor tissues. Our results show that pre-RC elements are significantly overexpressed in the majority of MB cell lines and tumor tissues. Notably, MCM10 shows the highest level of overexpression (~500-1000-fold) among all pre-RC mRNAs. In addition, siRNA-mediated silencing of MCM10 reduces cell viability, cell number and cell proliferation in MB cells. Taken together, our study provides evidence for deregulation of pre-RC elements in MB, and suggests that MCM10 is a potential therapeutic target for …show more content…
In a schwannoma tumor model, we demonstrated that genetically engineered EVs containing the suicide gene mRNA and protein-cytosine deaminase (CD) which is fused to uracil phosphoribosyltransferase (UPRT) reduced tumor growth in vivo. Glioblastoma is the most common primary brain tumor and highly aggressive with limited treatment options. Therefore we established a subcutaneous glioblastoma tumor model in mice to investigate if our approach can be used here as well. We implanted U87-MG cells into flanks of SCID mice followed by intratumoral injection with EVs, isolated either from cells expressing CD-UPRT or EGFP. Tumor growth was determined by caliper measurements after intraperitoneal administration of the prodrug 5-fluorocytosine. Here we showed a significantly reduced tumor growth in vivo after treatment with CDUPRT-enriched EVs. Taken together, our findings may be a useful tool for the treatment of glioblastoma with EVs carrying CD-UPRT
Medulloblastoma (MB) is one of the most malignant and frequent childhood brain tumors. Development of a non-invasive assay to detect MB in early stages might improve the life of many children. Accordingly, identification of circulating tumor biomarkers in MB patients would facilitate screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis for survival after clinical intervention. The transcription factor OTX2, which is normally silenced in the adult brain, is overexpressed in the majority of MBs (60-75%). In this study, we hypothesized that OTX2 mRNA encapsulated in extracellular vesicles (EVs) can serve as a non-invasive, early diagnostic and/or …show more content…
Overexpression of several pre-RC elements have been identified in different cancer types, including medulloblastoma (MB). Notably, overexpression of minichromosome maintenance (MCM) proteins 2, 3 and 7 is associated with migration and invasion in MB. In this study, we provide a more comprehensive mRNA expression profiling of a larger set of pre-RC elements in different MB cell lines and tumor tissues. Our results show that pre-RC elements are significantly overexpressed in the majority of MB cell lines and tumor tissues. Notably, MCM10 shows the highest level of overexpression (~500-1000-fold) among all pre-RC mRNAs. In addition, siRNA-mediated silencing of MCM10 reduces cell viability, cell number and cell proliferation in MB cells. Taken together, our study provides evidence for deregulation of pre-RC elements in MB, and suggests that MCM10 is a potential therapeutic target for …show more content…
In a schwannoma tumor model, we demonstrated that genetically engineered EVs containing the suicide gene mRNA and protein-cytosine deaminase (CD) which is fused to uracil phosphoribosyltransferase (UPRT) reduced tumor growth in vivo. Glioblastoma is the most common primary brain tumor and highly aggressive with limited treatment options. Therefore we established a subcutaneous glioblastoma tumor model in mice to investigate if our approach can be used here as well. We implanted U87-MG cells into flanks of SCID mice followed by intratumoral injection with EVs, isolated either from cells expressing CD-UPRT or EGFP. Tumor growth was determined by caliper measurements after intraperitoneal administration of the prodrug 5-fluorocytosine. Here we showed a significantly reduced tumor growth in vivo after treatment with CDUPRT-enriched EVs. Taken together, our findings may be a useful tool for the treatment of glioblastoma with EVs carrying CD-UPRT