Search results for "Blastoma"
showing 10 items of 603 documents
Oxidative modification impairs SERCA activity in Drosophila and human cell models of Parkinson's disease
2021
DJ-1 is a causative gene for familial Parkinson's disease (PD) with different functions, standing out its role against oxidative stress (OS). Accordingly, PD model flies harboring a mutation in the DJ-1β gene (the Drosophila ortholog of human DJ-1) show high levels of OS markers like protein carbonylation, a common post-translational modification that may alter protein function. To increase our understanding of PD pathogenesis as well as to discover potential therapeutic targets for pharmacological intervention, we performed a redox proteomic assay in DJ-1β mutant flies. Among the proteins that showed increased carbonylation levels in PD model flies, we found SERCA, an endoplasmic reticulum…
Antiproliferative Effect of Elastin-Derived Peptide VGVAPG on SH-SY5Y Neuroblastoma Cells
2019
Throughout the lifetime of humans, the amount of stem cells and the rate of cell proliferation continue to decrease. Reactive oxygen species (ROS) are one among the many factors that promote stem cell aging. Both a decrease in the level of stem cells and increase in ROS production can lead to the development of different neurodegenerative diseases. This study was conducted to determine how the VGVAPG peptide, liberated from elastin during the aging process and under pathological conditions, affects ROS production and activities of antioxidant enzymes in undifferentiated, proliferating SH-SY5Y cells. SH-SY5Y cells were maintained in Dulbecco’s modified Eagle’s medium/nutrient mixture F-12 su…
Inhibition of STAT3 with the generation 2.5 antisense oligonucleotide, AZD9150, decreases neuroblastoma tumorigenicity and increases chemosensitivity
2017
Abstract Purpose: Neuroblastoma is a pediatric tumor of peripheral sympathoadrenal neuroblasts. The long-term event-free survival of children with high-risk neuroblastoma is still poor despite the improvements with current multimodality treatment protocols. Activated JAK/STAT3 pathway plays an important role in many human cancers, suggesting that targeting STAT3 is a promising strategy for treating high-risk neuroblastoma. Experimental Design: To evaluate the biologic consequences of specific targeting of STAT3 in neuroblastoma, we assessed the effect of tetracycline (Tet)-inducible STAT3 shRNA and the generation 2.5 antisense oligonucleotide AZD9150 which targets STAT3 in three representat…
A Shotgun Proteomics Approach Reveals a New Toxic Role for Alzheimer's Disease Aβ Peptide: Spliceosome Impairment.
2017
Proteomic changes have been described in many neurodegenerative diseases, including Alzheimer's disease (AD). However, the early events in the onset of the pathology are yet to be fully elucidated. A cell model system in which LAN5 neuroblastoma cells were incubated for a short time with a recombinant form of Aβ42 was utilized. Proteins extracted from these cells were subjected to shotgun proteomics analysis by LTQ-Orbitrap-MS followed by label-free quantitation. By bioinformatics tools we found that the most significant of those found to be up-regulated were related to cytoskeletal dynamics (Rho related) and membrane-related processes. The most significant of the down-regulated proteins we…
Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma
2018
Since the proper activation of T cells requires the physical interaction with target cells through the formation of immunological synapses (IS), an alteration at this level could be a reason why tumors escape the immune response. As part of their life cycle, it is thought that T cells alternate between a static phase, the IS, and a dynamic phase, the immunological kinapse (IK), depending on high or low antigen sensing. Our investigation performed in tissue samples of human glioma shows that T cells are able to establish synapsing interactions not only with glioma tumorigenic cells, but also with stromal myeloid cells. Particularly, the IS displaying a T cell receptor-rich (TCR-rich) central…
Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis
2018
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium. E6 and E7 viral proteins are involved in the process of carcinogenesis. They interact with suppressors of oncogenesis, including p53 and Rb proteins. Th…
Rett Syndrome Mutant Neural Cells Lacks MeCP2 Immunoreactive Bands.
2016
Dysfunctions of MeCP2 protein lead to various neurological disorders such as Rett syndrome and Autism. The exact functions of MeCP2 protein is still far from clear. At a molecular level, there exist contradictory data. MeCP2 protein is considered a single immunoreactive band around 75 kDa by western-blot analysis but several reports have revealed the existence of multiple MeCP2 immunoreactive bands above and below the level where MeCP2 is expected. MeCP2 immunoreactive bands have been interpreted in different ways. Some researchers suggest that multiple MeCP2 immunoreactive bands are unidentified proteins that cross-react with the MeCP2 antibody or degradation product of MeCP2, while others…
11q Deletion or ALK Activity Curbs DLG2 Expression to Maintain an Undifferentiated State in Neuroblastoma
2020
High-risk 11q deleted neuroblastomas typically display undifferentiated/poorly differentiated morphology. Neuroblastoma is thought to develop from Schwann cell precursors and undifferentiated neural crest (NC) derived cells. It is therefore vital to understand mechanisms involved in the block of differentiation. We identify an important role for oncogenic ALK-ERK1/2-SP1 signaling in maintenance of undifferentiated NC-derived progenitors via repression of DLG2, a tumor suppressor in neuroblastoma. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors become chromaffin cells of the adrenal gland. We …
Rescue of Hypovitaminosis A Induces Non-Amyloidogenic Amyloid Precursor Protein (APP) Processing.
2015
Retinoic acid, the bioactive metabolite of beta-carotene or vitamin A, plays a pleiotropic, multifunctional role in vertebrate development. Studies in rodents revealed that a diet deficient in vitamin A results in a complex neonatal syndrome (the VAD syndrome), manifested in many organs. In humans, the function of retinoic acid (RA) extends into adulthood, where it has important roles in fertility, vision, and suppression of neoplastic growth. In recent years, it has also been suggested that retinoic acid might potentially act as a therapeutically relevant drug in attenuating or even preventing neurodegenerative diseases such as Alzheimer's disease (AD). Here, we report that VAD leads to an…
The soluble form of pan-RTK inhibitor and tumor suppressor LRIG1 mediates downregulation of AXL through direct protein–protein interaction in gliobla…
2019
Abstract Background Targeted approaches for inhibiting epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases (RTKs) in glioblastoma (GBM) have led to therapeutic resistance and little clinical benefit, raising the need for the development of alternative strategies. Endogenous LRIG1 (Leucine-rich Repeats and ImmunoGlobulin-like domains protein 1) is an RTK inhibitory protein required for stem cell maintenance, and we previously demonstrated the soluble ectodomain of LRIG1 (sLRIG1) to potently inhibit GBM growth in vitro and in vivo. Methods Here, we generated a recombinant protein of the ectodomain of LRIG1 (sLRIG1) and determined its activity in various cellular GBM mo…