Exosomes are nanometer-sized lipid vesicles released ubiquitously by cells, which have been shown to a normal physiological role, as well influence the tumor microenvironment and aid metastasis. Recent studies highlight ability of exosomes convey tumor-suppressive oncogenic mRNAs, microRNAs, proteins receiving cell, subsequently activating downstream signaling pathways influencing cellular phenotype. Here, we show that radiation increases abundance glioblastoma cells astrocytes. derived from...

Object. To overcome the problems associated with using stereotactic techniques to establish intracranial xenografts in nude mice and treat engrafted tumors intratumoral therapies (such as gene or viral therapies), authors developed an implantable guide-screw system. In this study, they describe system, its method of implantation, their experience establishing delivering therapy. Methods. The system consists a 2.6-mm guide screw central 0.5-mm diameter hole that accepts 26-gauge needle...

Abstract In vitro investigations of tumor stem-like cells (TSC) isolated from human glioblastoma (GB) surgical specimens have been done primarily at an atmospheric oxygen level 20%. To determine whether more consistent with in situ conditions affects their stem cell–like characteristics, we compared GB TSCs grown under 20% and 7% oxygen. Growing CD133+ sorted three neurosphere cultures O2 reduced doubling time increased the self-renewal potential as reflected by clonogenicity. Furthermore,...

Prostaglandins are arachidonate metabolites produced in virtually all mammalian tissues and possess diverse biologic capabilities, including vasoconstriction, vasodilatation, stimulation or inhibition of platelet aggregation, immunomodulation, primarily immunosupression (1–4). They implicated the promotion development growth malignant tumors (4–7). also involved response tumor normal to cytotoxic agents such as ionizing radiation (8). Prostaglandin production is mediated by two...

Abstract Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation for cancer therapy. Because HDAC modulates chromatin structure and gene expression, parameters considered to influence radioresponse, we have investigated the effects of inhibitor MS-275 on radiosensitivity two human tumor cell lines (DU145 prostate carcinoma U251 glioma). Acetylation status histones H3 H4 was determined as a function time after addition removal from culture medium. acetylation increased by 6 h...

Valproic acid (VA) is a well-tolerated drug used to treat seizure disorders and has recently been shown inhibit histone deacetylase (HDAC). Because HDAC modulates chromatin structure gene expression, parameters considered influence radioresponse, we investigated the effects of VA on radiosensitivity human brain tumor cells grown in vitro vivo. The cell lines SF539 U251 were our study. Histone hyperacetylation served as an indicator inhibition. assessed using clonogenic survival assay...

Abstract Purpose: CD133+ glioblastoma tumor stem-like cells (TSC) have been defined as radioresistant. However, although previously classified relative to CD133− cells, the radiosensitivity of TSCs with respect standard model, established glioma cell lines, has not determined. Therefore, better understand radioresponse this cancer stem cell, we used lines a framework for defining their in vitro radioresponse. Experimental Design: The intrinsic TSC cultures and was determined by clonogenic...

Abstract Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors are undergoing clinical evaluation for cancer therapy. Because PARP inhibition has been shown to enhance tumor cell sensitivity radiation, we investigated the in vitro and vivo effects of novel inhibitor E7016. Experimental Design: The effect E7016 on radiosensitivity lines was evaluated using clonogenic survival. DNA damage repair were measured γH2AX foci neutral comet assay. Mitotic catastrophe determined by immunostaining....

Brain tumor xenografts initiated from glioblastoma (GBM) CD133+ stem-like cells (TSCs) are composed of TSC and non-TSC subpopulations, simulating the phenotypic heterogeneity GBMs in situ. Given that discrepancies between radiosensitivity GBM vitro treatment response patients suggest a role for microenvironment radioresistance, we compared TSCs non-TSCs irradiated under orthotopic conditions. As measure radioresponse determined at individual cell level, γH2AX 53BP1 foci were quantified their...

Glioblastomas (GBMs) are characterized as highly invasive; the contribution of GBM stem-like cells (GSCs) to invasive phenotype, however, has not been completely defined. Towards this end, we have defined invasion potential CD133+ GSCs and their differentiated CD133− counterparts grown under standard in vitro conditions co-culture with astrocytes. Using a trans-well assay, astrocytes or astrocyte conditioned media bottom chamber significantly increased yet had no effect on cells. In...

Abstract Radiotherapy is a primary treatment modality for glioblastomas (GBM). Because DNA-PKcs critical factor in the repair of radiation-induced double strand breaks (DSB), this study evaluated potential VX-984, new inhibitor, to enhance radiosensitivity GBM cells. Treatment established cell line U251 and stem-like (GSC) NSC11 with VX-984 under vitro conditions resulted concentration-dependent inhibition phosphorylation. In similar manner, enhanced each as defined by clonogenic analysis....

Inhibitors of the molecular chaperone Hsp90 have been shown to enhance tumor cell radiosensitivity. To begin address mechanism responsible, we determined effect inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) on DNA damage response radiation. Exposure MiaPaCa cells 17DMAG, which results in radiosensitization, inhibited repair double-strand breaks according gammaH2AX foci dispersal and neutral comet assay. This inhibition was associated with reduced DNA-PK catalytic...

Histone deacetylase (HDAC) inhibitors are undergoing clinical evaluation in cancer therapy. Because HDAC modulation has been shown to enhance the radiosensitivity of tumor cells vitro, we investigated effects inhibitor MS-275 on radioresponse DU145 prostate carcinoma xenografts.As an indicator inhibition vivo, histone acetylation status lysates was determined after two, four, and six injections delivered at 12-hour intervals, as well 24 48 hours last injection. Tumor growth delay studies...

Abstract Vascular endothelial growth factor (VEGF) is an cell‐specific mitogen, which also enhances vascular permeability. Because this angiogenic has been suggested to play a role in brain tumor biology, we have begun investigate the regulation of VEGF expression cultures rat type I astrocytes. In report, focused on influence hypoxia expression. Under standard vitro conditions (21% O 2 ) astrocytes barely detectable by northern analysis. However, after exposure 0.2% for as little 3 h mRNA...

Although ionizing radiation has been shown to influence gene transcription, little is known about the effects of on translational efficiency. To obtain a genome-wide perspective translation, microarray analysis was done polysome-bound RNA isolated from irradiated human brain tumor cells; allow for comparison with also using total RNA. The number genes whose activity modified by approximately 10-fold greater than those transcription affected. radiation-induced change in gene's involve...

Abstract Purpose: Temozolomide, a DNA methylating agent, is currently undergoing clinical evaluation for cancer therapy. Because temozolomide has been shown to increase survival rates of patients with malignant gliomas when given combined radiation, and there conflicting preclinical data concerning the radiosensitizing effects temozolomide, we further investigated possible temozolomide-induced enhancement radiosensitivity. Experimental Design: The on in vitro radiosensitivity U251 (a human...