Etoposide-Bound Magnetic Nanoparticles Designed for Remote Targeting of Cancer Cells Disseminated Within Cerebrospinal Fluid Pathways.

Magnetic nanoparticles (MNPs) have potential for enhancing drug delivery in selected cancer patients, including those which have cells that have disseminated within cerebrospinal fluid (CSF) pathways. Here, we present data related to the creation and use of new two-part MNPs consisting of magnetic gold-iron alloy cores which have streptavidin binding sites, and are coated with biotinylated etoposide. Etoposide was chosen due to its previous use in the CSF and ease of biotinylation.

Cerebral Microdialysis as a Tool for Assessing the Delivery of Chemotherapy in Brain Tumor Patients.

The development of curative treatment for glioblastoma has been extremely challenging. Chemotherapeutic agents that have seemed promising have failed in clinical trials. Drugs that can successfully target cancer cells within the brain must first traverse the brain interstitial fluid.

Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery.

Background: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet.

Tumor Development and Angiogenesis in Adult Brain Tumor: Glioblastoma.

Angiogenesis is the growth of new capillaries from the preexisting blood vessels. Glioblastoma (GBM) tumors are highly vascularized tumors, and glioma growth depends on the formation of new blood vessels. Angiogenesis is a complex process involving proliferation, migration, and differentiation of vascular endothelial cells (ECs) under the stimulation of specific signals.

Elucidating the microRNA-203 specific biological processes in glioblastoma cells from comprehensive RNA-sequencing transcriptome profiling.

Glioblastoma (GBM) is the most common primary malignant intracranial adult brain tumor. Allelic deletion on chromosome 14q plays an essential role in GBM pathogenesis, and this chromosome 14q site was thought to harbor multiple tumor suppressor genes associated with GBM, a region that also encodes microRNA-203 (miR-203). This study was conducted to identify whole transcriptome profile changes associated with miR-203 expression by high-throughput RNA sequencing.

MicroRNAs in glioblastoma pathogenesis and therapy: A comprehensive review.

Glioblastoma (GBM), also known as grade IV astrocytoma, is the most aggressive primary intracranial tumor of the adult brain. MicroRNAs (miRNAs), a class of small non-coding RNA species, have critical functions across various biological processes. A great deal of progress has been made recently in dissecting miRNA pathways associated with the pathogenesis of GBM.

Matrix metalloproteinases: their functional role in lung cancer.

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM).

SPARC overexpression alters microRNA expression profiles involved in tumor progression.

Medulloblastoma is the most common malignant brain tumor in children. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in multiple processes in various cancers. Previously, we reported that SPARC expression significantly impairs medulloblastoma tumor growth and and also alters chemo sensitivity.

miR-let-7f-1 regulates SPARC mediated cisplatin resistance in medulloblastoma cells.

Our previous studies indicate that Secreted Protein Acidic and Rich in Cysteine (SPARC) expression suppressed medulloblastoma tumor growth in vitro and in vivo. Here we sought to determine the effect of SPARC expression in medulloblastoma cells to chemotherapeutic agents. In this study, we show that SPARC expression induces cisplatin resistance in medulloblastoma cells.

Molecular mechanisms underlying the divergent roles of SPARC in human carcinogenesis.

Communication between the cell and its surrounding environment, consisting of proteinaceous (non-living material) and extracellular matrix (ECM), is important for biophysiological and chemical signaling. This signaling results in a range of cellular activities, including cell division, adhesion, differentiation, invasion, migration and angiogenesis. The ECM non-structural secretory glycoprotein called secreted protein, acidic and rich in cysteine (SPARC), plays a significant role in altering cancer cell activity and the tumor's microenvironment (TME).

MicroRNA 203 Modulates Glioma Cell Migration via Robo1/ERK/MMP-9 Signaling.

Glioblastoma (GBM) is the most common and malignant primary adult brain cancer. Allelic deletion on chromosome 14q plays an important role in the pathogenesis of GBM, and this site was thought to harbor multiple tumor suppressor genes associated with GBM, a region that also encodes microRNA-203 (miR-203). In this study, we sought to identify the role of miR-203 as a tumor suppressor in the pathogenesis of GBM.

Blockade of SOX4 mediated DNA repair by SPARC enhances radioresponse in medulloblastoma.

SPARC is a matricellular glycoprotein and a putative radioresistance-reversal-gene. We therefore explored the possibility of SPARC expression on medulloblastoma radiosensitivity in vitro and in vivo. The combined treatment of the SPARC and irradiation resulted in increased cell death when compared to cells treated with irradiation alone in vitro and in vivo.

SPARC expression induces cell cycle arrest via STAT3 signaling pathway in medulloblastoma cells.

Dynamic cell interaction with ECM components has profound influence in cancer progression. SPARC is a component of the ECM, impairs the proliferation of different cell types and modulates tumor cell aggressive features. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo.

SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho-Rac-Cdc42.

The matricellular glycoprotein Secreted Protein Acidic and Rich in Cysteine (SPARC) plays an important role in the regulation of cell adhesion and proliferation as well as in tumorigenesis and metastasis. Earlier, we reported that, in addition to its potent anti-angiogenic functions, SPARC also induces apoptosis in medulloblastoma cells, mediated by autophagy. We therefore sought to investigate the underlying molecular mechanism through which SPARC inhibits migration and invasion of Daoy medulloblastoma cells, both in vitro and in vivo.

SPARC stimulates neuronal differentiation of medulloblastoma cells via the Notch1/STAT3 pathway.

Secreted protein acidic and rich in cysteine (SPARC) participates in the regulation of morphogenesis and cellular differentiation through its modulation of cell-matrix interactions. We previously reported that SPARC expression significantly impairs medulloblastoma tumor growth in vivo. In this study, we show that adenoviral-mediated overexpression of SPARC cDNA (Ad-DsRed-SP) elevated the expression of the neuronal markers NeuN, nestin, neurofilament, and MAP-2 in medulloblastoma cells and induced neuron-like differentiation.

Suppression of MMP-2 attenuates TNF-α induced NF-κB activation and leads to JNK mediated cell death in glioma.

Background: Abrogation of apoptosis for prolonged cell survival is essential in cancer progression. In our previous studies, we showed the MMP-2 downregulation induced apoptosis in cancer cell lines. Here, we attempt to investigate the exact molecular mechanism of how MMP-2 depletion leads to apoptosis in glioma xenograft cell lines.

Downregulation of uPA/uPAR inhibits intermittent hypoxia-induced epithelial-mesenchymal transition (EMT) in DAOY and D283 medulloblastoma cells.

Hypoxia is known to induce overexpression of the urokinase plasminogen activator (uPA) and its receptor (uPAR) and thus overexpression promotes uPAR-mediated survival signaling in various cancers. Moreover, hypoxia/ overexpression of uPAR in cancer cells promote the epithelial-mesenchymal transition (EMT) and thereby invasiveness and metastasis. In this study, we show that intermittent hypoxia has a more pronounced effect than chronic hypoxia and contributes to EMT, invasion and migration in medulloblastoma cells.

Suppression of uPA and uPAR attenuates angiogenin mediated angiogenesis in endothelial and glioblastoma cell lines.

Background: In our earlier reports, we showed that downregulation of uPA and uPAR inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited angiogenesis in nude mice. The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood.

Methodology/principal Findings: In the present study, we have attempted to investigate the mechanism by which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and glioblastoma cell lines.

Urokinase plasminogen activator receptor and/or matrix metalloproteinase-9 inhibition induces apoptosis signaling through lipid rafts in glioblastoma xenograft cells.

Small interfering RNA (siRNA)-mediated transcriptional knockdown of urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9), alone or in combination, inhibits uPAR and/or MMP-9 expression and induces apoptosis in the human glioblastoma xenograft cell lines 4910 and 5310. siRNA against uPAR (pU-Si), MMP-9 (pM-Si), or both (pUM-Si) induced apoptosis and was associated with the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase. Furthermore, protein levels of the Fas receptor (APO-1/CD-95) were increased following transcriptional inactivation of uPAR and/or MMP-9.

MMP-9, uPAR and cathepsin B silencing downregulate integrins in human glioma xenograft cells in vitro and in vivo in nude mice.

Background: Involvement of MMP-9, uPAR and cathepsin B in adhesion, migration, invasion, proliferation, metastasis and tumor growth has been well established. In the present study, MMP-9, uPAR and cathepsin B genes were downregulated in glioma xenograft cells using shRNA plasmid constructs and we evaluated the involvement of integrins and changes in their adhesion, migration and invasive potential.

Methodology/principal Findings: MMP-9, uPAR and cathepsin B single shRNA plasmid constructs were used to downregulate these molecules in xenograft cells.