Search results for " cytotoxic"
showing 10 items of 315 documents
Antimetastatic Effect of Immunization with Liposome-Encapsulated Tumor Cell-Membrane Proteins Obtained from Experimental Tumors
1995
Immunization of C57BL/6 mice with tumor-derived membrane-proteins encapsulated in sized liposomes (0.2 microgram/mouse) and composed by phosphatidylcholine or sphingomyelin, significantly reduced the mean values of spontaneous lung metastasis from both B16 (0.7 +/- 0.5 and 1.2 +/- 0.6, respectively) and 3LL (4.8 +/- 2.5 and 7.2 +/- 4.1, respectively) tumors, with respect to control (HEPES) groups (4.8 +/- 1.1 and 19.0 +/- 4.4, respectively). However, no significant antimetastatic effect was observed using free tumor-derived proteins (2 micrograms/mouse) or liposome vehicle alone. Specific humoral immune response after the vaccination was studied by flow cytometry of tumor cells incubated wi…
Inhibition of lymphocyte trafficking shields the brain against deleterious neuroinflammation after stroke
2011
T lymphocytes are increasingly recognized as key modulators of detrimental inflammatory cascades in acute ischaemic stroke, but the potential of T cell-targeted therapy in brain ischaemia is largely unexplored. Here, we characterize the effect of inhibiting leukocyte very late antigen-4 and endothelial vascular cell adhesion molecule-1-mediated brain invasion-currently the most effective strategy in primary neuroinflammatory brain disease in murine ischaemic stroke models. Very late antigen-4 blockade by monoclonal antibodies improved outcome in models of moderate stroke lesions by inhibiting cerebral leukocyte invasion and neurotoxic cytokine production without increasing the susceptibilit…
Phenotypical and functional analysis of memory and effector human CD8 T cells specific for mycobacterial antigens
2006
Abstract Mycobacterium tuberculosis infects one-third of the global population and claims two million lives every year. Because memory CD8 T cells exhibit a high heterogeneity in terms of phenotype and functional characteristic, we investigated the frequency, phenotype, and functional properties of Ag85A epitope-specific HLA-A*0201 CD8 T cells in children affected by tuberculosis (TB) before and 4 mo after chemotherapy and healthy contact children. Using Ag85A peptide/HLA-A*0201 pentamer, we found a low frequency of blood peptide-specific CD8 T cells in tuberculous children before therapy, which consistently increased after therapy to levels detected in healthy contacts. Ex vivo analysis of…
Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines
2015
CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectab…
Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigat…
2004
Abstract Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-( d -2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O (Alk=Me, n -Bu), while structural information has been gained by FT-IR, 119 Sn Mossbauer and 1 H, 13 C, 119 Sn NMR data. In particular, IR results suggested polymeric structures both for Alk 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating th…
Processing and MHC class I presentation of human cytomegalovirus pp65-derived peptides persist despite gpUS2–11-mediated immune evasion
2007
Immune control of human cytomegalovirus (HCMV) infection can be mediated by CD8+cytolytic T lymphocytes (CTL). Adoptive transfer of antiviral CTL confers protection against HCMV reactivation and disease. The tegument protein pp65 and the immediate-early 1 protein (IE1) are recognized to be major CTL targets, even though during productive infection the viral immunoevasion proteins gpUS2–11 act to suppress major histocompatibility complex (MHC) class I-restricted antigen presentation. Thus it was not clear how infected cells could be labelled with antigenic peptides in the face of immunoevasion. We show here that the immunodominant peptide pp65NLVwas presented by MHC class I in cells infected…
Mammalian cell growth on gold nanoparticle-decorated substrates is influenced by the nanoparticle coating
2014
In this work, we study epithelial cell growth on substrates decorated with gold nanorods that are functionalized either with a positively charged cytotoxic surfactant or with a biocompatible polymer exhibiting one of two different end groups, resulting in a neutral or negative surface charge of the particle. Upon observation of cell growth for three days by live cell imaging using optical dark field microscopy, it was found that all particles supported cell adhesion while no directed cell migration and no significant particle internalization occurred. Concerning cell adhesion and spreading as compared to cell growth on bare substrates after 3 days of incubation, a reduction by 45% and 95%, …
Proliferation and MHC-unrestricted bystander lysis by virus-specific cytotoxic T cells following antigen self-presentation.
1998
Cytotoxic T cells (CTL) not only act as effector cells, but can also serve as antigen-presenting cells (APC) for other CTL due to their expression of major histocompatibility complex (MHC) class I molecules. In the present study we show that independently derived CTL lines (CTLL) with specificity for an L(d)-presented nonapeptide corresponding to amino acids 168-176 of the immediate-early 1 (IE1) protein of murine cytomegalovirus not only lyse syngeneic but also allogeneic target cells, if the peptide is present during the cytolytic assay. Whereas a short peptide pulse is sufficient to render syngeneic cells susceptible to lysis, continued presence of soluble peptide is mandatory for the ly…
Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones
2004
In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 v…
2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands
2013
Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D-2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated…