Evaluation of Bacteriophage ϕ11 host recognition protein and its host-binding peptides for diagnosing/targeting of Saphylococcus aureus infections.

Evaluating the potential of using both synthetic and biological products as targeting agents for the diagnosis, imaging, and treatment of infections due to particularly antibiotic-resistant pathogens is important for controlling infections. We examined the interaction between Gp45, a receptor-binding protein of the ϕ11 lysogenic phage, and its host S. aureus, a common cause of nosocomial infections. Using molecular dynamics and docking simulations, we identified the peptides that bind to S. aureus wall teichoic acids via Gp45. We compared the binding affinity of Gp45 and the two highest-scoring peptide sequences (P1 and P3) and their scrambled forms using microscopy, spectroscopy, and ELISA. Our results revealed that rGp45 (recombinant Gp45) and chemically synthesized P1 had a higher binding affinity for S. aureus compared with all other peptides, with the exception of E. coli. Furthermore, rGp45 had a capture efficiency of over 86%; P1 had a capture efficiency of over 64%. Overall, our findings suggest that receptor-binding proteins such as rGp45, which provide a critical initiation of the phage life cycle for host adsorption, might play an important role in the diagnosis, imaging, and targeting of bacterial infections. Studying such proteins could accordingly enable the development of effective strategies for controlling infections.

Related mechanisms, current treatments, and new perspectives in meningioma.

Meningiomas are non-glial tumors that are the most common primary brain tumors in adults. Although meningioma can possibly be cured with surgical excision, variations in atypical/anaplastic meningioma have a high recurrence rate and a poor prognosis. As a result, it is critical to develop novel therapeutic options for high-grade meningiomas. This review highlights the current histology of meningiomas, prevalent genetic and molecular changes, and the most extensively researched signaling pathways and therapies in meningiomas. It also reviews current clinical studies and novel meningioma treatments, including immunotherapy, microRNAs, cancer stem cell methods, and targeted interventions within the glycolysis pathway. Through the examination of the complex landscape of meningioma biology and the highlighting of promising therapeutic pathways, this review opens the way for future research efforts aimed at improving patient outcomes in this prevalent intracranial tumor entity.

Investigating the Effects of Chordoma Cell-Derived Exosomes on the Tumorigenicity of Nucleus Pulposus Cells.

Objective Interaction of tumor cells with the surrounding environment is essential for tumor growth and progression that eventually leads to metastasis. Growing evidence shows that extracellular vesicles also known as exosomes play a crucial role in signaling between the tumor and its microenvironment. Tumor-derived exosomes have generally protumorigenic effects such as metastasis, hypoxia, angiogenesis, and epithelial-mesenchymal transition. Methods In this study, exosomes were isolated from a chordoma cell line, MUG-Chor1, and characterized subsequently. The number of exosomes was determined and introduced into the healthy nucleus pulposus (NP) cells for 140 days. The protumorigenic effects of a chordoma cell line-derived exosomes that initiate the tumorigenesis on NP cells were investigated. The impact of tumor-derived exosomes on various cellular events including cell cycle, migration, proliferation, apoptosis, and viability has been studied by treating NP cells with chordoma cell-line-derived exosomes cells. Results Upon treatment with exosomes, the NP cells not only gained a chordoma-like morphology but also molecular characteristics such as alterations in the levels of certain gene expressions. The migratory and angiogenic capabilities of NP cells increased after treatment with chordoma-derived exosomes. Conclusion Based on our findings, we can conclude that exosomes carry information from tumor cells and may exert tumorigenic effects on nontumorous cells.

Identification of Reference Genes in Chordoma Cells Allows Cross-Comparison of Expression Studies Across Subtypes.

AIM: To present the best housekeeping genes including clival/sacral based chordoma, and the nucleus pulposus cells. MATERIAL AND METHODS: We investigated 13 candidate reference genes in public chordoma array transcriptome datasets, validated these genes by using RT-PCR, and evaluated their stability with NormFinder, geNorm, and Bestkeeper. RESULTS: YWHAZ, TBP and PGK1 genes were identified as the most stable reference genes as confirmed with three different approaches. Conversely, KRT8, KRT19 and GAPDH genes are less stable and not appropriate for use in chordoma research. CONCLUSION: For normalization of RT-PCR experiments in gene profiling of chordoma, we recommend the use of the stable genes YWHAZ, TBP and PGK1.

NANOG Dominates Interleukin-6-Induced Sphere Formation in Prostate Cancer.

OBJECTIVE: Identifying the dynamics of prostate tumor aggressiveness is essential to find new therapeutics for the treatment. Cancer stem cells contribute to cancer progression by promoting tumor growth and metastasis, resisting treatment, and evading the immune system. Interleukin 6 (IL-6) is a pleiotropic cytokine that functions in inflammation, immune response, etc. However, dysregulated expression of IL-6 plays a pathological role in such conditions as cancer. In this study, we aimed to elucidate the effect of IL-6 on cancer stemness genes in prostate cancer cells. METHODS: Enrichment of stem-like cells was achieved through the formation of tumor spheres using the DU-145 cell line. Sphere formation was conducted in a medium supplemented with IL-6 and compared to a control group. The number of spheres was quantified, and the resulting pellet was collected for quantitative reverse transcription polymerase chain reaction analysis to assess the impact of IL-6 induction on the expression of stemness-related genes. RESULTS: Tumor sphere numbers and sizes increased in IL-6-induced environment. NANOG expression elevated in an IL-6-enriched environment compared to the nontreated spheres. Our results demonstrated that IL-6 induction in prostate tumor spheres upregulates NANOG gene expression. CONCLUSION: Inducing IL-6 in prostate tumor spheres stimulates stemness biomarker NANOG genes. NANOG may be suggested as a therapeutic target for metastatic prostate cancer.

Activation of Wnt Pathway Suppresses Growth of MUG-Chor1 Chordoma Cell Line.

Chordoma as a malignant bone tumor, occurs along the axial skeleton and does not have an effective therapy. Brachyury, which is a crucial player for the formation of early embryonic notochord, is abundantly found in both sporadic and familial chordoma. During embryonic development, Brachyury expression was reported to be regulated by the Wnt pathway. The objective of the study is to investigate the role of Wnt signaling in a human chordoma cell line in terms of proliferation, survival, and invasiveness. We tried to elucidate the signaling events that regulate Chordoma cancer. In this regard, Wnt pathway was activated or inhibited using various strategies including small molecules, siRNA-based knockdown and overexpression applications. The results indicated the negative regulatory effect of Wnt signaling activity on proliferation and migration capacity of the chordoma cells. It was revealed that when GSK3ß was inhibited, the Wnt pathway was activated and negatively regulated T/Bra expression. Activity of the Wnt pathway caused cell cycle arrest, reduced migration potential of the cells, and led to cell death. Therefore, the present study suggests that the Wnt pathway plays a key role in suppressing the proliferation and invasive characteristics of human chordoma cells and has a great potential as a therapeutic target in further clinical studies.

Impact of silencing eEF2K expression on the malignant properties of chordoma.

BACKGROUND: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. METHODS: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. RESULTS: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. CONCLUSION: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.

Preclinical Studies on Convalescent Human Immune Plasma-Derived Exosome: Omics and Antiviral Properties to SARS-CoV-2.

The scale of the COVID-19 pandemic forced urgent measures for the development of new therapeutics. One of these strategies is the use of convalescent plasma (CP) as a conventional source for passive immunity. Recently, there has been interest in CP-derived exosomes. In this report, we present a structural, biochemical, and biological characterization of our proprietary product, convalescent human immune plasma-derived exosome (ChipEXO), following the guidelines set forth by the Turkish Ministry of Health and the Turkish Red Crescent, the Good Manufacturing Practice, the International Society for Extracellular Vesicles, and the Gene Ontology Consortium. The data support the safety and efficacy of this product against SARS-CoV-2 infections in preclinical models.

miRNAs as cell fate determinants of lateral and paraxial mesoderm differentiation from embryonic stem cells.

To date, the role of miRNAs on pluripotency and differentiation of ESCs into specific lineages has been studied extensively. However, the specific role of miRNAs during lateral and paraxial mesoderm cell fate decision is still unclear. To address this, we firstly determined miRNA profile of mouse ESCs differentiating towards lateral and paraxial lineages which were detected using Flk1 and PDGFαR antibodies, and of myogenic and hematopoietic differentiation potential of purified paraxial and lateral mesodermal cells within these populations. miRNAs associated with lateral and paraxial mesoderm, and their targets were identified using bioinformatics tools. The targets of the corresponding miRNAs were validated after transfection into mouse ESCs. The roles of the selected miRNAs in lateral, and paraxial mesoderm formation were assessed along with hematopoietic and myogenic differentiation capacity. Among the miRNAs, mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p, upregulated in lateral mesoderm cells, and mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p, upregulated in paraxial mesoderm cells. While transient co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p increased the number of lateral mesodermal cells, co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p increased the number of paraxial mesodermal cells. Moreover, differentiation potential of the lateral mesodermal cells into hematopoietic cell lineage increased upon co-transfection of mmu-miR-126a-3p, mmu-miR-335-5p and mmu-miR-672-5p and differentiation potential of the paraxial mesodermal cells into skeletal muscle lineage were increased upon co-transfection of mmu-miR-10b-5p, mmu-miR-196a-5p and mmu-miR-615-3p. In conclusion, we determined the miRNA profile of lateral and paraxial mesodermal cells and co-transfection of miRNAs increased differentiation potential of both lateral and paraxial mesodermal cells transiently.

E-cadherin might be a stage-dependent modulator in aggressiveness in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) pathology is known for its uncontrollable progress due to highly invasive characteristics and refractory behavior against existing chemotherapies. The aberrant expression of CDH1 (expresses the protein E-cadherin) is associated with increased overall survival in various cancers, however, E-cadherin expression in PDAC progression has remained elusive. We investigated the impact of exogenously elevated E-cadherin levels on the tumorigenicity of transduced low grade and metastatic PDAC cell lines, Panc-1 and AsPC-1, respectively. Constitutive expression of E-cadherin promoted a more hybrid E/M state in AsPC-1 cells, while it was associated with the acquisition of a more epithelial-like state in Panc1 cells. Our study suggests that E-cadherin may play differential roles in determining the metastatic characteristics of primary and metastatic pancreatic cancer cells.

Inhibition of Migration, Invasion and Drug Resistance of Pancreatic Adenocarcinoma Cells - Role of Snail, Slug and Twist and Small Molecule Inhibitors.

PURPOSE: The main purpose of this study is to demonstrate the effects of epithelial to mesenchymal transition activating transcription factor silencing (EMT-ATF silencing) on migration, invasion, drug resistance and tumor-forming abilities of various pancreatic cancer cell lines. Additionally, the contribution of small molecule inhibitors of EMT (SD-208 and CX4945) to the effects of gene silencing was evaluated. METHODS: EMT activating transcription factors "Snail, Slug and Twist" were silenced by short hairpins on Panc-1, MIA PaCa-2, BxPC-3, and AsPC-1 pancreatic cancer cell lines. The changes in migration, invasion, laminin attachment, cancer stem-like cell properties and tumor-forming abilities were investigated. Chemosensitivity assays and small molecule inhibitors of EMT were applied to the metastatic pancreatic cancer cell line AsPC-1. RESULTS: EMT-ATF silencing reduced EMT and stem cell-like characteristics of pancreatic cancer cell lines. Following EMT-ATF silencing amongst the four PC cell lines, AsPC-1 showed the best response and was chosen for further chemoresistance and combinational therapy applications. EMT downregulated AsPC-1 cells showed less resistance to select chemotherapeutics compared to the control group. Both small molecule inhibitors enhanced the outcomes of EMT-ATF silencing. CONCLUSION: Overall it was found that EMT-ATF silencing, either by EMT-ATF silencing or with the enhancement by small molecules, is a good candidate to treat pancreatic cancer since it simultaneously minimizes metastasis, stem cell properties, and drug resistance.

The role of TNF-α in chordoma progression and inflammatory pathways.

PURPOSE: Chordomas are highly therapy-resistant primary bone tumors that exhibit high relapse rates and may induce local destruction. Here, we evaluated the effects of tumor necrosis factor-alpha (TNF-α) on chordoma progression and clinical outcome. METHODS: Chordoma cells were treated with TNF-α after which its short- and long-term effects were evaluated. Functional assays, qRT-PCR and microarray-based expression analyses were carried out to assess the effect of TNF-α on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, invasion and cancer stem cell-like properties. Finally, relationships between TNF-α expression and clinicopathological features were assessed in a chordoma patient cohort. RESULTS: We found that TNF-α treatment increased the migration and invasion of chordoma cells. Also, NF-κB activation was observed along with increased EMT marker expression. In addition, enhanced tumor sphere formation and soft agar colony formation were observed, concomitantly with increased chemo-resistance and CD338 marker expression. The TNF-α and TNFR1 expression levels were found to be significantly correlated with LIF, PD-L1 and Ki67 expression levels, tumor volume and a short survival time in patients. In addition, a high neutrophil to lymphocyte ratio was found to be associated with recurrence and a decreased overall survival. CONCLUSIONS: From our data we conclude that TNF-α may serve as a prognostic marker for chordoma progression and that tumor-promoting inflammation may be a major factor in chordoma tumor progression.

Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance.

Chordoma is a rare, slow-growing tumor thought to arise from remnants of embryonic notochord associated with an aggressive outcome. Cancer stem-like cells (CSCs) are related to tumorigenesis, recurrence, and resistance in cancers. Therefore, chordoma CSCs are possible targets for chordoma treatment. In this study, dysregulated miRNAs were determined in chordoma CSCs and identified their role in chordoma. Dysregulated miRNAs were determined via miRNA microarray and validated through qPCR. miRNAs were transiently transfected to the chordoma cell lines and their roles in proliferation, apoptosis, migration and invasion capacities and stem-like properties were identified. Finally, a relationship between clinicopathological features and dysregulated miRNAs has been evaluated among 21 chordoma patients. CD133+CD15+ cells exhibited CSC phenotype with increased CSC- and Epithelial-Mesenchymal Transition (EMT)-related gene expression, invasion, migration, tumorosphere- and colony-forming abilities. In addition, WNT5A, TGF-α, BTG2 and MYCBP genes involved in CSC-related pathways, were targets of miR-140-3p, miR-148a-3p, miR-210-5p and miR-574-5p, respectively. Transfection of CSC-related miRNAs also increased migration and invasion along with stem cell phenotype. Finally, we determined that miR-140-3p and miR-148a-3p expressions correlated with Ki67 while miR-140-3p and TGF-α expressions were correlated with p53. Moreover, MYCBP expression was positively correlated with tumor volume, and metastasis was associated with the expression of miR-210-5p and TGF-α in our patient cohort. Through these findings, we conclude that chordoma CSCs have distinctive miRNA profile, which can regulate stem-like properties of chordoma CSCs.

Co-polysomy of 1p/19q in glial tumors: Retrospective analysis of 221 cases from single center.

Glial tumors are malignant brain tumors that arise from glial cells of brain or spine and have genetic aberrations in their genome. 1p/19q co-deletion is associated with increased Overall Survival (OS) time with enhanced response to chemo- and radio-therapy in oligodendrogliomas. However, prognostic significance of 1p/19q co-polysomy is still unclear. We evaluated 1p/19q status of 221 patients with glial tumor by Fluorescent in situ Hybridization (FISH). Records of the patients were collected retrospectively. Our results demonstrated that 1p/19q co-polysomy was associated with decreased OS time, high P53 expression and frequently located in temporal lobe, whereas 1p/19q co-deletion was associated with increased overall survival time, low P53 expression and frontal lobe location. Furthermore, classification of patients based on both 1p/19q status and P53 expression revealed that patients with 1p/19q co-polysomy and high P53 expression had the worst prognosis. Lastly, our bioinformatic survival analysis revealed that high expression of SRM, ICMT, and FTL located in 1p36.13-p36.31 and 19q13.2-q13.33 region were related with decreased OS time in patients with Low Grade Glioma (LGG). The study demonstrated that 1p/19q co-polysomy is a poor prognostic marker for glial tumor.

Smooth muscle cell differentiation from rabbit amniotic cells.

Amniotic fluid (AF) is the liquid layer that provides mechanical support and allows movement of the fetus during embryogenesis. Mesenchymal stem cells (MSCs), which have differentiation capacity, are also found in AF-derived cells at a low ratio. Smooth muscle cells (SMCs) play an important role in organ function and are frequently used in tissue engineering. We examined the differentiation of AF-derived MSCs (AMSCs) into SMCs. AMSCs were sorted from cultured amniotic cells and differentiated into SMCs using differentiation agents, including platelet-derived growth factor BB (PDGF-BB) and tumor growth factor ß (TGF-ß). Characterization of differentiated SMCs was confirmed morphologically, molecularly (via quantitative polymerase chain reaction [qPCR] and immunocytochemistry [ICC]), and functionally (using a contractile assay and fluo-4 calcium signaling assay). Poly(lactide-co-glycolide) (PLGA) scaffolds were fabricated, and the attachment capacity of AMSCs was assessed via scanning electron microscopy. AMSCs were successfully differentiated into SMCs. Our results indicate that AMSCs change their morphology and exhibit increased expression of ACTA2 and MYH11, which was confirmed via qPCR and ICC. Furthermore, functional experiments revealed that differentiated SMCs had both contraction ability and increased Ca2 concentration in the cytoplasm. Finally, PLGA scaffolds were prepared and AMSCs were successfully planted onto the scaffolds. The AMSCs fully differentiated into functional SMCs, and the PLGA polymer is a suitable scaffold material for AMSCs. With further clinical trials, AF-derived MSC-based SMC engineering may become a highly efficient treatment option.

Simultaneous miRNA and mRNA transcriptome profiling of glioblastoma samples reveals a novel set of OncomiR candidates and their target genes.

Although glioblastomas are common, there remains a need to elucidate the underlying mechanisms behind their initiation and progression and identify molecular pathways for improving treatment. In this study, sixteen fresh-frozen glioblastoma samples and seven samples of healthy brain tissues were analyzed with miRNA and whole transcriptome microarray chips. Candidate miRNAs and mRNAs were selected to validate expression in fifty patient samples in total with the criteria of abundance, relevance and prediction scores. miRNA and target mRNA relationships were assessed by inhibiting selected miRNAs in glioblastoma cells. Functional tests have been conducted in order to see the effects of miRNAs on invasion, migration and apoptosis of GBM cells. Analyses were carried out to determine correlations between selected molecules and clinicopathological features. 1332 genes and 319 miRNAs were found to be dysregulated by the microarrays. The results were combined and analyzed with Transcriptome Analysis Console 3 software and the DAVID online database. Primary differential pathways included Ras, HIF-1, MAPK signaling and cell adhesion. OncomiR candidates 21-5p, 92b-3p, 182-5p and 339-5p for glioblastoma negatively correlated with notable mRNA targets both in tissues and in in vitro experiments. miR-21-5p and miR-339-5p significantly affected migration, invasion and apoptosis of GBM cells in vitro. Significant correlations with overall survival, tumor volume, recurrence and age at diagnosis were discovered. In this article we present valuable integrated microarray analysis of glioblastoma samples regarding miRNA and gene-expression levels. Notable biomarkers and miRNA-mRNA interactions have been identified, some of which correlated with clinicopathological features in our cohort.

Identification of An mtDNA Setpoint Associated with Highest Levels of CD44 Positivity and Chemoresistance in HGC-27 and MKN-45 Gastric Cancer Cell Lines.

OBJECTIVE: Cancer stem cells (CSCs) have important roles in survival and chemoresistance. These cells are commonly recognized with CD44 and CD24 markers. In this study, we aimed to analyze the effects of mtDNA content on cell surface positivity for anti-CD24 and anti-CD44 antibodies and chemoresistance level in AGS, HGC-27 and MKN-45 gastric cancer (GC) cell lines and to determine a setpoint for mtDNA copy for each cell line. MATERIALS AND METHODS: In this experimental study, we initially decreased mtDNA levels in AGS, HGC-27 and MKN-45 by EtBr treatment. This depletion was confirmed with quantitative polymerase chain reaction (qPCR). Changes in cell surface positivity for anti-CD24 and anti-CD44 antibodies in control and mtDNA-depleted AGS, HGC-27 and MKN-45 were then analyzed with flow cytometry. Changes in chemoresistance (5-FU and cisplatin) were analyzed for all cell lines. The relationship between mtDNA content and cell surface positivity for CD24 and CD44 markers was examined. RESULTS: The highest CD44 positivity was found in HGC-27 and MKN-45 ρlow cells which had 33-40% mtDNA content of control cells, however, CD24 positivity decreased with mtDNA depletion in all cell lines. The highest chemoresistance levels were found in all ρlow cells. mtDNA-recovered (i.e. reverted) HGC-27 and MKN-45 cells partially maintained their increased chemoresistance while reverted AGS cells did not maintain an increased level of chemoresistance. CONCLUSION: mtDNA depletion triggers chemoresistance in cancer cell lines and is correlated with increase and decrease of CD44 and CD24 positivity respectively in HGC-27 and MKN-45 GC cell lines. A mtDNA content above or below the identified setpoint (33-40% of that in control cells), results in the decrease of CD44 positivity and chemoresistance levels.

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fibroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

The effect of TWIST silencing in metastatic chordoma cells.

Chordoma is a slowly growing and invasive bone tumor  with a tendency to metastasize locally in advanced stages.  It is essential to discover new therapeutics that target genes involved in the metastasis of chordoma. Epithelial-mesenchymal transition (EMT) might robustly influence the metastasis of a tumor bulk. To our knowledge, this is the first time to show that EMT might have a role in chordoma metastasis. In this study, we aim to investigate the possible role of Twist, a key player transcription factor of EMT, in chordoma metastasis. The TWIST gene was silenced by short hairpins in chordoma cell line MUG-Chor1 and effects on metastasis were investigated by wound healing/gap closure and invasion assays. Twist-silenced MUG-Chor1 cells were found to be less migratory and less invasive when compared to the negative control. This study indicates that Twist might have a role in metastatic chordoma cells.

Boron nitride nanotubes for gene silencing.

BACKGROUND: Non-viral gene delivery is increasingly investigated as an alternative to viral vectors due to low toxicity and immunogenicity, easy preparation, tissue specificity, and ability to transfer larger sizes of genes. METHODS: In this study, boron nitride nanotubes (BNNTs) are functionalized with oligonucleotides (oligo-BNNTs). The morpholinos complementary to the oligonucleotides attached to the BNNTs (morpholino/oligo-BNNTs) are hybridized to silence the luciferase gene. The morpholino/oligo-BNNTs conjugates are administered to luciferase-expressing cells (MDA-MB-231-luc2) and the luciferase activity is monitored. RESULTS: The luciferase activity is decreased when MDA-MB-231-luc2 cells were treated with morpholino/oligo-BNNTs. CONCLUSIONS: The study suggests that BNNTs can be used as a potential vector to transfect cells. GENERAL SIGNIFICANCE: BNNTs are potential new nanocarriers for gene delivery applications.