Search results for "Cytotoxic"
showing 10 items of 1673 documents
The sequence alteration associated with a mutational hotspot in p53 protects cells from lysis by cytotoxic T lymphocytes specific for a flanking pept…
1998
A high proportion of tumors arise due to mutation of the p53 tumor suppressor protein. A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues 264–272, renders cells resistant to killing by human histocompatibility leukocyte antigen (HLA)-A*0201–restricted cytotoxic T lymphocytes (CTLs) specific for this epitope. Acquisition of the R to H mutation at residue 273 of the human p53 protein promotes tumor growth in vivo by selective escape from recognition by p53.264–272 peptide-specific CTLs. Synthetic 27-mer p53 polypeptides covering the antigenic nonamer region 264–272 of p53 were used as proteasome substrates to investigate whether the R…
Anti H-2Dd alloreactivity mediated by herpes-simplex-virus specific cytotoxic H-2k T lymphocytes is associated with H-2Dk.
1980
Herpes-simplex-virus (HSV) specific, H-2k-restricted, immune cytotoxic T lymphocytes also lyse noninfected H-2d target cells. Genetic mapping studies revealed that HSV-specific Dk-restricted CTL cross-react with allogeneic targets expressing Dd alloantigens. Cold target inhibition experiments indicate that only a minority of HSV-specific CTL mediate cross-reactive cytolysis. The data give an example of where the phenomenon of H-2-restricted versus nonrestricted responsiveness is not due to distinct subsets of T cells but solely depends on the antigenic determinants recognized.
Influenza virus-specific T cell-mediated cytotoxicity: integration of the virus antigen into the target cell membrane is essential for target cell fo…
1979
This study deals with the requirements for target cell recognition by influenza A virus-specific cytotoxic T lymphocytes (CTL). H-2-identical cells were incubated with infectious or UV light-inactivated influenza A virus expressing either cleaved or uncleaved hemagglutinin (HA). Thereafter, the treated cells were tested in a 4-h 51Cr assay for susceptibility to CTL-mediated cytolysis. Regardless whether the influenza virus was infectious, virions expressing cleaved HA were efficient in target cell formation. In contrast, cells incubated with either active or UV-inactivated virions expressing uncleaved HA were not lysed by virus-specific CTL. Yet, after mere trypsin-mediated cleavage of the …
Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines
2019
The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparti…
When the functionalisation comes in useful: ionic liquids with a “sweet” appended moiety demonstrate drastically reduced toxicological effects
2020
The growing number of applications of ionic liquids (ILs) in industry have brought attention to the green credentials of synthesis, as well as their cytotoxicities and ecotoxicities both for their use and accidental leakage into the environment. With the abovementioned properties in mind, we designed a class of ILs with either cations bearing a gluconamide motif and aliphatic side chains or the anion incorporating a gluconic acid (derived from food waste) moiety. An IL with an imidazolium cation with an appended gluconic amide (bearing five hydroxyl groups) moiety was also synthesized for a useful comparison. Different structural features were considered, placing emphasis on the nature and …
Synthesis, chemical characterization, computational studies and biological activity of new DNA methyltransferases (DNMTs) specific inhibitor. Epigene…
2015
This work deals with the synthesis, the chemical characterization of dibutyltin(IV) complex of caffeic acid (Bu2Sn(IV)HCAF, caf1) and its cytotoxic action on tumor cells. The coordination environment at the tin center was investigated by FTIR, (119)Sn{(1)H} cross polarization magic angle spinning, electrospray ionization mass spectroscopy in the solid state and UV-vis, fluorescence and (1)H, (13)C and (119)Sn NMR spectroscopy in solution phases. Density functional theory study confirmed the proposed structures in solution phase and indicated the most probably stable conformation. The effects on viability of breast cancer MDA-MB231, colorectal cancer HCT116, hepatocellular carcinoma HepG2 an…
Ras-Related GTPase RhoB Forces Alkylation-Induced Apoptotic Cell Death
2000
rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments. To address the question of the physiological role of RhoB in cellular defense, cells stably overexpressing wild-type RhoB protein were generated. Overexpression of RhoB renders cells hypersensitive to the killing effect of alkylating agents including antineoplastic drugs but not to UV-light and doxorubicin. As compared to control cells, RhoB overexpressing cells revealed an increase in the frequency of alkylation-induced apoptotic cell death. This indicates that RhoB is involved in modulating apoptotic signaling. Furthermore, overexpression of RhoB resulted in a prolonged transient block to DNA replicat…
Photoinduced DNA damage efficiency and cytotoxicity of novel viologen linked pyrene conjugates.
2010
Novel viologen linked pyrene conjugates permeate cells efficiently and exhibit spacer length dependent DNA damage and cytotoxicity upon photoexcitation.
Checkpoint adaptation in repair-deficient cells drives aneuploidy and resistance to genotoxic agents
2018
AbstractHuman cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ repair-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge. We demonstrate that adaptation inhibition, eit…
Phytochemical profile and bioactivity of traditional ayurvedic decoctions and hydro-alcoholic macerations of Boerhaavia diffusa L. and Curculigo orch…
2015
Decoctions (DECs) and hydro-alcoholic extracts (HEs) prepared from roots of Boerhaavia diffusa L. (Nyctaginaceae) and Curculigo orchioides Gaertn. (Hypoxidaceae) were phytochemically characterised by HPLC-DAD and profiled for their antioxidant, antigenotoxic and cytotoxic activities. B. diffusa DEC was rich in ferulic acid and vanillin, while the HE also contained boeravinone B and eupalitin. Both C. orchioides HE and DEC displayed the main occurrence of orcinol-β-d-glucoside and curculigoside A. Antioxidant activity was assayed through spectrophotometric DPPH, ABTS and β-carotene bleaching test, and using (HP)TLC bioautographic strategies. For both crude drugs, HE was the best performing p…