Search results for "Cytotoxic"
showing 10 items of 1673 documents
Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.
2020
An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secret…
Could formaldehyde induce mutagenic and cytotoxic effects in buccal epithelial cells during anatomy classes?
2017
Background Due to increased formaldehyde exposure, carcinogenic to humans, several researches have been studying the potential toxicity and the safe levels for human beings. The aim of this study was to investigate mutagenicity and cytotoxicity in buccal epithelial exfoliated cells (BEC) of students subjected to formaldehyde (FA) during anatomy classes. Material and Methods BEC were collected periodically from 17 volunteers of undergraduate programs, who had participated in practical anatomy classes, before and after FA exposure. Cells were stained according to Feulgen method and then micronucleus test was applied. A total of 1,500 cells were assessed per individual in this study for the mi…
Microenvironment in neuroblastoma: isolation and characterization of tumor-derived mesenchymal stromal cells
2018
Background It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment. Methods Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. …
In vitro evaluation of a biomaterial-based anticancer drug delivery system as an alternative to conventional post-surgery bone cancer treatment
2018
Patients diagnosed with osteosarcoma are currently treated with intravenous injections of anticancer agents after tumor resection. However, due to remaining neoplastic cells at the site of tumor removal, cancer recurrence often occurs. Successful bone regeneration combined with the control of residual cancer cells presents a challenge for tissue engineering. Cyclodextrins loaded with chemotherapeutic drugs reversibly release the drugs over time. Hydroxyapatite bone biomaterials coated with doxorubicin-loaded cyclodextrin should release the drug with time after implantation directly at the original tumor site and may be a way to eliminate residual neoplastic cells. In the present study, we h…
Silver Atomic Quantum Clusters of Three Atoms for Cancer Therapy: Targeting Chromatin Compaction to Increase the Therapeutic Index of Chemotherapy
2018
Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag3 -AQCs)-developed by an ad hoc method-augment chromatin accessibility. This effect only occurs during DNA replication. Coadministration of Ag3 -AQCs increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag3 -AQCs increases the amount of cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tiss…
Positive Role of the MHC Class-I Antigen Presentation Regulator m04/gp34 of Murine Cytomegalovirus in Antiviral Protection by CD8 T Cells
2020
Murine cytomegalovirus (mCMV) codes for MHC class-I trafficking modulators m04/gp34, m06/gp48, and m152/gp40. By interacting with the MHC class-Iα chain, these proteins disconnect peptide-loaded MHC class-I (pMHC-I) complexes from the constitutive vesicular flow to the cell surface. Based on the assumption that all three inhibit antigen presentation, and thus the recognition of infected cells by CD8 T cells, they were referred to as “immunoevasins.” Improved antigen presentation mediated by m04 in the presence of m152 after infection with deletion mutant mCMV-Δm06W, compared to mCMV-Δm04m06 expressing only m152, led us to propose renaming these molecules “viral regulators of antigen present…
The Anti-apoptotic Murine Cytomegalovirus Protein vMIA-m38.5 Induces Mast Cell Degranulation.
2020
Mast cells (MC) represent "inbetweeners" of the immune system in that they are part of innate immunity by acting as first-line sentinels for environmental antigens but also provide a link to adaptive immunity by secretion of chemokines that recruit CD8 T cells to organ sites of infection. An interrelationship between MC and cytomegalovirus (CMV) has been a blank area in science until recently when the murine model revealed a role for MC in the resolution of pulmonary infection by murine CMV (mCMV). As to the mechanism, MC were identified as a target cell type of mCMV. Infected MC degranulate and synthesize the CC-chemokine ligand-5 (CCL-5), which is released to attract protective virus-spec…
New Synthetic Nitro-Pyrrolomycins as Promising Antibacterial and Anticancer Agents
2020
: Pyrrolomycins (PMs) are polyhalogenated antibiotics known as powerful biologically active compounds, yet featuring high cytotoxicity. The present study reports the antibacterial and antitumoral properties of new chemically synthesized PMs, where the three positions of the pyrrolic nucleus were replaced by nitro groups, aiming to reduce their cytotoxicity while maintaining or even enhancing the biological activity. Indeed, the presence of the nitro substituent in diverse positions of the pyrrole determined an improvement of the minimal bactericidal concentration (MBC) against Gram-positive (i.e., Staphylococcus aureus) or -negative (i.e., Pseudomonas aeruginosa) pathogen strains as compare…
Immunodominant Cytomegalovirus Epitopes Suppress Subdominant Epitopes in the Generation of High-Avidity CD8 T Cells
2021
CD8+ T-cell responses to pathogens are directed against infected cells that present pathogen-encoded peptides on MHC class-I molecules. Although natural responses are polyclonal, the spectrum of peptides that qualify for epitopes is remarkably small even for pathogens with high coding capacity. Among those few that are successful at all, a hierarchy exists in the magnitude of the response that they elicit in terms of numbers of CD8+ T cells generated. This led to a classification into immunodominant and non-immunodominant or subordinate epitopes, IDEs and non-IDEs, respectively. IDEs are favored in the design of vaccines and are chosen for CD8+ T-cell immunotherapy. Using murine cytomegalov…
An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019
2020
Abstract Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.