Search results for "Coma"

2-Methoxyestradiol Affects Mitochondrial Biogenesis Pathway and Succinate Dehydrogenase Complex Flavoprotein Subunit A in Osteosarcoma Cancer Cells.

2017

Background/aim Dysregulation of mitochondrial pathways is implicated in several diseases, including cancer. Notably, mitochondrial respiration and mitochondrial biogenesis are favored in some invasive cancer cells, such as osteosarcoma. Hence, the aim of the current work was to investigate the effects of 2-methoxyestradiol (2-ME), a potent anticancer agent, on the mitochondrial biogenesis of osteosarcoma cells. Materials and methods Highly metastatic osteosarcoma 143B cells were treated with 2-ME separately or in combination with L-lactate, or with the solvent (non-treated control cells). Protein levels of α-syntrophin and peroxisome proliferator-activated receptor gamma, coactivator 1 alph…

Exploiting Gangliosides for the Therapy of Ewing’s Sarcoma and H3K27M-Mutant Diffuse Midline Glioma

2021

Simple Summary Osteosarcoma, Ewing’s sarcoma, and H3K27M-mutant diffuse midline glioma are rare but aggressive malignancies occurring mainly in children. Due to their rareness and often fatal course, drug development is challenging. Here, we repurposed the existing drugs dinutuximab and eliglustat and investigated their potential to directly target or indirectly modulate the tumor cell-specific ganglioside GD2. Our data suggest that targeting and/or modulating tumor cell-specific GD2 may offer a new therapeutic strategy for the above mentioned tumor entities. Abstract The ganglioside GD2 is an important target in childhood cancer. Nevertheless, the only therapy targeting GD2 that is approve…

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma : the oncogenic role of the ligands

2017

Altres ajuts: This work was supported by grants from Institut Català d'Oncologia (ICO), Instituto de Salud Carlos III (RTICC-RD12/0036/0016, /0020, /0035, /0057; and PI14/00647), Fundació A BOSCH, Fundació Amics Joan Petit, ajuts predoctorals del VHIR and RIS3CAT grants COMRDI15-1-0014 (ACCIÓ and FEDER). Altres ajuts: FEDER/COMRDI15-1-0014 Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional …

c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells

2018

Mesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs express…

Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol–induced neuronal nitric oxide synthase uncoupling in met…

2020

Abstract 2-methoxyestradiol (2-ME) is a physiological anticancer compound, metabolite of 17β-estradiol. Previously, our group evidenced that from mechanistic point of view one of anticancer mechanisms of action of 2-ME is specific induction and nuclear hijacking of neuronal nitric oxide synthase (nNOS), resulting in local generation of nitro-oxidative stress and finally, cancer cell death. The current study aims to establish the substantial mechanism of generation of reactive nitrogen species by 2-ME. We further achieved to identify the specific reactive nitrogen species involved in DNA-damaging mechanism of 2-ME. The study was performed using metastatic osteosarcoma 143B cells. We detected…

2019

Purpose: Clear resection margins are paramount for good outcome in children undergoing solid tumor resections. Multiphoton microscopy (MPM) can provide high-resolution, real-time, intraoperative microscopic images of tumor tissue. Objective: This prospective international multicenter study evaluates the diagnostic accuracy, feasibility, and interobserver congruence of MPM in diagnosing solid pediatric tissue and tumors for the first time. Material and methods: Representative fresh sections from six different neonatal solid tissues (liver, lung, kidney, adrenal gland, heart muscle, testicle) and two types of typical pediatric solid tumors (neuroblastoma, rhabdomyosarcoma) with adjacent nonne…

Risk of Classic Kaposi Sarcoma With Combinations of Killer Immunoglobulin-Like Receptor and Human Leukocyte Antigen Loci: A Population-Based Case-con…

2015

BACKGROUND Kaposi sarcoma (KS) is a complication of KS-associated herpesvirus (KSHV) infection. Other oncogenic viral infections and malignancies are associated with certain HLA alleles and their natural killer (NK) cell immunoglobulin-like receptor (KIR) ligands. We tested whether HLA-KIR influences the risk of KSHV infection or KS. METHODS In population-based case-control studies, we compared HLA class I and KIR gene frequencies in 250 classic (non-AIDS) KS cases, 280 KSHV-seropositive controls, and 576 KSHV-seronegative controls composing discovery and validation cohorts. Logistic regression was used to calculate sex- and age-adjusted odds ratios (ORs) and 95% confidence intervals. RESUL…

Autoimmune aspects in glaucoma

2016

The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Studies demonstrate changes of autoantibody concentrations against retinal and optic nerve head antigens in glaucoma patients. Furthermore we found antibody deposits in human glaucomatous retinae in a pro-inflammatory environment. Clinical studies showed up regulated, but also significantly down-regulated autoantibody levels. These antibodies belong to the natural autoimmunity. The upregulation of autoantibodies can be associated with fatal conditions, but several studies demonstrate that natural autoantibodies entail also neuroprotective characteristics and influence the protein expression …

Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells

2016

Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 an…

Course of serum autoantibodies in patients after acute angle-closure glaucoma attack

2017

Background The aim of our current investigation was to analyze the autoantibody -reactivities of patients after acute angle closure glaucoma (AACG) by means of a protein microarray approach to identify intraocular pressure (IOP)-dependent antibodies. Methods Collected sera from different study time points (AACG n = 6, 0, 2, 4 and 12 weeks) and control group (CTRL n = 11, 0 and 12 weeks) were analyzed. Protein-microarrays were incubated with sera and occurring immunoreactivities were visualized with fluorescence labeled anti-human-IgG antibodies. To detect changes, spot intensities were digitized and compared with statistical techniques. Results Three autoantibodies with significant level-al…