silicon and Brain-Neoplasms

Approximately 80% of brain tumours are gliomas. Despite treatment, patient mortality remains high due to local metastasis and relapse. It has been shown that transferrin-functionalised porous silicon nanoparticles (Tf@pSiNPs) can inhibit the migration of U87 glioma cells. However, the underlying mechanisms and the effect of glioma cell heterogeneity, which is a hallmark of the disease, on the efficacy of Tf@pSiNPs remains to be addressed.. Here, we observed that Tf@pSiNPs inhibited heterogeneous patient-derived glioma cells' (WK1) migration across small perforations (3 μm) by approximately 30%. A phenotypical characterisation of the migrated subpopulations revealed that the majority of them were nestin and fibroblast growth factor receptor 1 positive, an indication of their cancer stem cell origin. The treatment did not inhibit cell migration across large perforations (8 μm), nor cytoskeleton formation. This is in agreement with our previous observations that cellular-volume regulation is a mediator of Tf@pSiNPs' cell migration inhibition. Since aquaporin 9 (AQP9) is closely linked to cellular-volume regulation, and is highly expressed in glioma, the effect of AQP9 expression on WK1 migration was investigated. We showed that WK1 migration is correlated to the differential expression patterns of AQP9. However, AQP9-silencing did not affect WK1 cell migration across perforations, nor the efficacy of cell migration inhibition mediated by Tf@pSiNPs, suggesting that AQP9 is not a mediator of the inhibition.. This in vitro investigation highlights the unique therapeutic potentials of Tf@pSiNPs against glioma cell migration and indicates further optimisations that are required to maximise its therapeutic efficacies.

Topics: Aquaporins; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Glioblastoma; Glioma; Humans; Nanoparticles; Neoplastic Stem Cells; Porosity; Receptor, Fibroblast Growth Factor, Type 1; Silicon

Application of micro-Raman spectroscopy for the monitoring of quality of nanowire sensor chips fabrication has been demonstrated. Nanowire chips have been fabricated on the basis of «silicon-on-insulator» (SOI) structures (SOI-NW chips). The fabrication of SOI-NW chips was performed by optical litography with gas-phase etching. The so-fabricated SOI-NW chips are intended for highly sensitive detection of brain cancer biomarkers in humans. In our present study, two series of experiments have been conducted. In the first experimental series, detection of a synthetic DNA oligonucleotide (oDNA) analogue of brain cancer-associated microRNA miRNA-363 in purified buffer solution has been performed in order to demonstrate the high detection sensitivity. The second experimental series has been performed in order to reveal miRNA-363 itself in real human plasma samples. To provide detection biospecificity, the SOI-NW chip surface was modified by covalent immobilization of probe oligonucleotides (oDNA probes) complementary to the target biomolecules. Using the SOI-NW sensor chips proposed herein, the concentration detection limit of the target biomolecules at the level of 3.3 × 10

Topics: Biosensing Techniques; Brain Neoplasms; Humans; MicroRNAs; Nanowires; Plasma; Quality Control; Silicon; Spectrum Analysis, Raman

Tumor angiogenesis is a complex process that is unamenable to intravital whole-process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging-optical coherence tomography angiography (OCTA)-laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo-chemotherapy of tumor by monitoring blood oxygen saturation (SaO

Topics: Animals; Antimetabolites, Antineoplastic; Brain Neoplasms; Disease Models, Animal; Fluorouracil; Glioma; Humans; Male; Mice; Mice, Inbred BALB C; Multimodal Imaging; Nanostructures; Oxygen Saturation; Photoacoustic Techniques; Silicon; Tomography, Optical Coherence

Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.

Topics: Apoptosis; Brain Neoplasms; Cell Movement; Cell Proliferation; Drug Delivery Systems; Extracellular Space; Glioblastoma; Humans; Nanoparticles; Porosity; Silicon; Transferrin; Tumor Cells, Cultured

Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence.. Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO.. NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only.. These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.

Topics: Animals; Antineoplastic Agents, Alkylating; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Combined Modality Therapy; Glioma; Humans; Hyperbaric Oxygenation; Hyperthermia, Induced; Mice, Nude; Nanoparticles; Neoplasm Transplantation; Neoplastic Stem Cells; Particle Size; Porosity; Rats; Silicon; Temozolomide

Cranioplasty is a well-known procedure, and autologous graft bone is usually considered the best choice in this procedure, but it cannot be used in conditions such as bone-infiltrating tumors, spheno-orbital en plaque meningiomas, and bone infections. Polymethylmethacrylate (PMMA) offers great possibility of intraoperative adaption. We describe a case of 1-step cranioplasty performed in a patient with a meningeal fibrosarcoma using a custom-made silicon mold.. A 48-year-old man was admitted to our department for a left temporo-parietal subcutaneous tumefaction that grew for a few months on the site of a previous osteodural decompression. After a biopsy that was diagnostic for meningeal fibrosarcoma, we planned tumor asportation, considering the bone infiltration of the tumor and the necessity of a cranioplasty. Before the intervention, we performed the craniotomy on a gypsum powder head phantom created based on a computed tomography scan. Then, using a computer-assisted design technique, a silicon mold was created and sterilized for the intervention. The edges of the preoperative simulated craniectomy were reproduced during the intervention using a rigid rail on the patient's scalp. The craniectomy was performed, and the tumor was removed. Then, a PMMA bone flap was made using a silicon mold and was fixed to the skull by miniscrews. Aesthetic results were considered excellent by the patient.. We performed a 1-step cranioplasty after resection of a meningeal fibrosarcoma that infiltrated bone with a new technique to reproduce during intervention a preoperative simulated craniectomy and a computer-assisted design PMMA flap.

Topics: Brain Neoplasms; Craniotomy; Fibrosarcoma; Humans; Inventions; Male; Meningeal Neoplasms; Middle Aged; Phantoms, Imaging; Plastic Surgery Procedures; Polymethyl Methacrylate; Silicon; Skull Neoplasms

Porous silicon nanoparticles (pSiNPs) with tunable pore size are biocompatible and biodegradable, suggesting that they are suitable biomaterials as vehicles for drug delivery. Loading of small interfering RNA (siRNA) into the pores of pSiNPs can protect siRNA from degradation as well as improve the cellular uptake. We aimed to deliver MRP1 siRNA loaded into pSiNPs to glioblastoma cells, and to demonstrate downregulation of MRP1 at the mRNA and protein levels.. 50-220 nm pSiNPs with an average pore size of 26 nm were prepared, followed by electrostatic adsorption of siRNA into pores. Oligonucleotide loading and release profiles were investigated; MRP1 mRNA and protein expression, cell viability and cell apoptosis were studied.. Approximately 7.7 µg of siRNA was loaded per mg of pSiNPs. Cells readily took up nanoparticles after 30 min incubation. siRNA-loaded pSiNPs were able to effectively downregulate target mRNA (~40%) and protein expression (31%), and induced cell apoptosis and necrosis (33%).. siRNA loaded pSiNPs downregulated mRNA and protein expression and induced cell death. This novel siRNA delivery system may pave the way towards developing more effective tumor therapies.

Topics: Base Sequence; Brain Neoplasms; Cell Line, Tumor; DNA Primers; Glioblastoma; Humans; Microscopy, Electron, Scanning; Nanoparticles; RNA, Small Interfering; Silicon; Spectrometry, Mass, Secondary Ion; Static Electricity

Primary brain tumors are among the most deadly of all cancers, with a 1-year survival rate of 52%. Certain elements, such as nickel, cadmium, chromium, arsenic, and beryllium, are established carcinogens in other organs. Silicon and titanium are suspected carcinogens and other elements are known to promote or inhibit the rate of tumor growth. Knowledge about the carcinogenicity of these elements in the brain is limited. In this study, we investigated the potential role of these elements as risk factors for human brain tumors.. In a case-control study, we assessed brain biopsies from 12 patients with various types of primary brain tumors and in tumor-free brain tissue from 6 autopsy cases. We used energy-dispersive X-ray analysis (EDX) to determine if there were significant differences in the concentration of the study elements in tumors and in control brains.. In a bivariate analysis, a statistically significant association was observed between the presence of brain tumors and the concentrations of silicon (p = 0.01), magnesium (p = 0.01), and calcium (p = 0.03). Zinc was also associated with a borderline significance (p = 0.05). No association was observed for nickel (p = 0.74). Although the magnitude of the observed association was estimated using multiple logistic regression analyses, the relative risk estimates were imprecise because of insufficient sample size. Further research using a larger sample size is needed to elucidate the role of these elements in human brain carcinogenesis.

Topics: Aged; Brain Neoplasms; Case-Control Studies; Chlorine; Electron Probe Microanalysis; Environmental Exposure; Female; Humans; Male; Metals; Middle Aged; Occupational Exposure; Risk Factors; Silicon

To investigate the relation of aluminum and silicon in drinking water to risk of Alzheimer's disease, we carried out a case-control study in eight regions of England and Wales. Subjects were identified from the records of neuroradiology centers, and diagnoses were confirmed by a review of hospital case-notes. Exposure to aluminum and silicon in drinking water was estimated from residential histories of 106 men with Alzheimer's disease, 99 men with other dementing illnesses, 226 men with brain cancer, and 441 men with other diseases of the nervous system. All subjects in the study were between 42 and 75 years of age. There was little association between Alzheimer's disease and higher aluminum or lower silicon concentrations in drinking water when cases were compared with any of the control groups. The results indicate that any risk of Alzheimer's disease from aluminum in drinking water at concentrations below 0.2 mg per liter is small, and they give no support for a protective role of silicon.

Topics: Adult; Aged; Aluminum; Alzheimer Disease; Brain Neoplasms; Case-Control Studies; Dementia; England; Humans; Male; Middle Aged; Risk Factors; Silicon; Wales; Water Pollutants; Water Supply

Topics: Acute Disease; Adolescent; Adult; Aged; Brain Neoplasms; Cerebral Hemorrhage; Cerebrovascular Disorders; Humans; Ischemic Attack, Transient; Middle Aged; Silicon