Search results for " T cell"
showing 10 items of 1161 documents
Abstract 857: Metal oxide nanoparticles as adjuvant for radiation therapy
2018
Abstract Background: Radiation therapy comprises a fundamental component of modern tumor treatment. Unfortunately, its success is limited by the development of radiation resistances. The emerging field of nanotechnology offers great opportunities for diagnosing, imaging, as well as treating cancer. Metal oxide nanoparticles in particular zinc oxide nanoparticles (ZnO-NP) have been shown to display a selective cytotoxic effect on tumor cells via a yet unknown mechanism. Most likely the generation of reactive oxygen species (ROS), breakdown of mitochondria and DNA damage are involved. The success of radiation therapy equally relies on the generation of ROS, which develop their cytotoxic poten…
An Immunogenic Peptide Derived from NM23-H2 Is Expressed on Bcr/abl+ Cells.
2006
Abstract Objective: Most tumors express antigens which, when presented by MHC molecules, can be recognized by cytotoxic T-lymphocytes. These tumor-associated-antigens (TAA) are considered to be key determinants in the graft-versus-tumor effect after allogeneic hematopoietic cell transplantation (HCT) and are therefore potential candidates for tumor vaccination. Unfortunately only small numbers of TAA have been isolated to date. In this project we looked for immunogenic peptides presented by bcr/abl+ cells of an HLA-A32 CML patient. Methods: Leukemia-specific mixed lymphocyte leukemia cell cultures (MLLC) were generated by co-culturing irradiated bcr/abl+ cells from the patient with peripher…
Isopetasin and S-isopetasin as novel P-glycoprotein inhibitors against multidrug-resistant cancer cells
2019
Abstract Background A major problem of cancer treatment is the development of multidrug resistance (MDR) to chemotherapy. MDR is caused by different mechanisms such as the expression of the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). These transporters efflux xenobiotic toxins, including chemotherapeutics, and they were found to be overexpressed in different cancer types. Purpose Identification of novel molecules that overcome MDR by targeting ABC-transporters. Methods Resazurin reduction assay was used for cytotoxicity test. AutoDock 4.2. was used for molecular docking. The function of P-gp and BCRP was tested using a doxorubicin …
Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expre…
2019
Abstract Background In the drug discovery field, natural products deemed a precious source of novel lead compounds. They have the ability to bypass or overcome multidrug resistance (MDR) in cancer cells. Purpose In this study, the natural polyphenolic stilbene resveratrol (RES) has been studied for its cytotoxic activity toward MDR cancer cells. Methods Resazurin assay was used to investigate the cytotoxicity of RES not only against a panel of drug-resistant cancer cells overexpressing P-glycoprotein/ABCB1, BCRP/ABCG2, ABCB5 (ATP-binding cassette transporters), but also mutation-activated EGFR. The assessment of proteins expression was done by Western blot analysis. COMPARE and hierarchical…
Human ABCB1 confers cells resistance to cytotoxic guanidine alkaloids from Pterogyne nitens.
2015
Multidrug resistance (MDR) caused by human ABCB1 (P-glycoprotein/MDR1) is one of the major obstacles in chemotherapy. To understand the mechanism of MDR by ABCB1 and circumvent the MDR, in the present study, we established human ABCB1-expressing cells (Flp-In-293/ABCB1 cells) and examined the cytotoxic effects of four guanidine alkaloids from Pterogyne nitens (galegine, nitensidine A, pterogynidine and pterogynine) using Flp-In-293/Mock and Flp-In-293/ABCB1 cells. The activity of ABCB1 in Flp-In-293/ABCB1 cells were confirmed by typical substrates for ABCB1 (taxol and vinblastine) in MTT assay. Flp-In-293/ABCB1 cells were also resistant to the four guanidine alkaloids as well as taxol and v…
The effect of the interferon-γ-inducible processing machinery on the generation of a naturally tumor-associated human cytotoxic T lymphocyte epitope …
2002
The human wild-type (wt) p53.264–272 peptide is a universal tumor antigen and recognized by HLA-A*0201 (A2.1)-restricted CTL. Generation of this epitope by constitutive 20S proteasomes is prevented by a p53 R to H hotspot mutation at the C-terminal flanking residue 273. We report on the impact of the interferon-γ (IFN-γ)-inducible proteasomal activator PA28 (11S regulator) and the immunoproteasome on the in vitro and cellular processing of wt and mutant (mut) p53 substrates. We found that production of the antigenic 264–272 peptide from wt p53 by constitutive as well as immunoproteasomes is accelerated and amplified by the PA28 activator. PA28 and (immuno)proteasomes were not capable to rec…
Targeting Acute Leukemia and Cancer by High-Affinity T-Cell-Receptor Transfer
2003
Accumulation and subsequent overexpression of human mdm2 (hdm2) and altered p53 protein is associated with high-level presentation of hdm2 and wild-type (wt) p53 derived peptides by major histocompatibility complex (MHC) class I molecules on a wide range of malignant cells. A major barrier to the design of broad-spectrum hdm2 and p53 specific immunotherapeutics for leukemia and cancer, however, has been the observation that low-level expression of hdm2 and wt p53 peptides by non-transformed tissues and cells results in self-tolerance of T-lymphocytes with high avidity for self-class I MHC / self-peptide complexes. Although the peripheral T-cell repertoire is mostly devoid of such high-avidi…
Biology and management of therapy-related acute promyelocytic leukemia.
2013
Therapy-related acute promyelocytic leukemia (t-APL) has been increasingly reported after exposure to cytotoxic and/or immunosuppressive agents given for prior malignancies or autoimmune diseases. t-APL represents both a model for better understanding human leukemogenesis and an interesting therapeutic subset which requires specific adaptations for optimal management.We discuss here potential risk factors for t-APL development and the main biologic and clinical characteristics of t-APL as compared to de-novo APL.In addition, we review therapeutic results obtained in patients with t-APL receiving conventional retinoic acid and chemotherapy and discuss new treatment opportunities with minimal…
Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway.
2014
Abstract Dendritic cells (DC) are one target for immune suppression by regulatory T cells (Treg), because their interaction results in reduced T cell stimulatory capacity and secretion of inhibitory cytokines in DC. We show that DC in the presence of Treg are more mobile as compared with cocultures with conventional CD4+ T cells and form DC–Treg aggregates within 2 h of culture. The migration of DC was specifically directed toward Treg, as Treg, but not CD4+ T cells, attracted DC in Boyden chambers. Treg deficient for the ectonucleotidase CD39 were unable to attract DC. Likewise, addition of antagonists for A2A adenosine receptors abolished the formation of DC–Treg clusters, indicating a ro…
Aminobisphosphonates as new weapons for gammadelta T Cell-based immunotherapy of cancer.
2008
BACKGROUND: Activated V gamma 9 V delta 2 T cells are able to kill most tumour cells because of recognition by T cell receptor and natural killer receptors. OBJECTIVE: We discuss the possibility that the intentional activation of gammadelta T cells in vivo by aminobisphosphonates may represent a promising target for the design of novel and highly innovative immunotherapy in cancer patients. METHODS: The antitumoral effects of gammadelta T cells both in vitro and in vivo have been demonstrated suggesting a new therapeutic approach for translation into the clinical setting. RESULTS/CONCLUSION: V gamma 9 V delta 2 T lymphocytes represent a particularly interesting target for immunotherapeutic …