ABSTRACT
We studied the effect of low and high-dose rate photon radiation on activation of cell death by apoptosis and necrosis in malignant cell lines of lymphocytic origin Raji and Jurkat (human B and T-cell lymphomas) and normal human lymphocytes from healthy volunteers. It was shown that photon radiation with ultra-high dose rate induced significantly higher levels of "early" apoptosis and lower levels of necrosis compared to γ-radiation with dose rate used for radiation therapy.
Subject(s)
Apoptosis/radiation effects , Gamma Rays , Lymphocytes/radiation effects , Cell Line, Tumor , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Humans , Jurkat Cells , Lymphocytes/pathology , Necrosis/pathology , Primary Cell CultureABSTRACT
We described two original genetic constructs encoding chimeric monomolecular T-cell receptors, where the effector T-cell receptor fragment was linked with the antigen-recognizing part consisting of two variable fragments of two different antibodies to carcinoembryonic antigen. Following transfection, these receptors were expressed on the cell surface and bound carcinoembryonic antigen. Human peripheral blood lymphocytes transfected with the above constructs demonstrated high cytotoxic activity against HCT116 cells expressing carcinoembryonic antigen.
Subject(s)
Carcinoembryonic Antigen/immunology , Cytotoxicity, Immunologic , Receptors, Antigen, T-Cell/metabolism , Recombinant Fusion Proteins/metabolism , Cell Survival , HCT116 Cells , HEK293 Cells , HT29 Cells , Humans , Immunotherapy , Neoplasms/immunology , Neoplasms/therapy , Receptors, Antigen, T-Cell/genetics , Recombinant Fusion Proteins/genetics , TransfectionABSTRACT
The study was concerned with antitumor action of internalized peptide incorporating a fragment of p161INK4a using a model of short-lived human tumor cultures sampled from resected material. Renal cancer sample showed the greatest therapeutic interval.
Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinase Inhibitor p16/pharmacology , Neoplasms/drug therapy , Antineoplastic Agents/metabolism , Antineoplastic Agents/therapeutic use , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclin-Dependent Kinase Inhibitor p16/therapeutic use , Humans , Kidney Neoplasms/drug therapy , Neoplasms/metabolism , Time Factors , Tumor Cells, CulturedABSTRACT
Properties of chimeric peptides containing cell-penetrating sequences and pl6INK4a and E2F fragments were studied in vitro on immurtal cultures of human cells. Both sequences exhibit cytostatic activity. The peptide containing fragment p16INK4a inhibited proliferation during the G0/G1 stage of the cell cycle, while sequence E2F suppressed proliferation in S phase. Both sequences exhibit cytotoxic properties and can induce apoptosis.
Subject(s)
Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclins/antagonists & inhibitors , Cytostatic Agents/metabolism , E2F1 Transcription Factor/metabolism , Peptide Fragments/metabolism , Recombinant Fusion Proteins/metabolism , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p16/genetics , E2F1 Transcription Factor/genetics , Humans , Peptide Fragments/genetics , Recombinant Fusion Proteins/geneticsABSTRACT
The study is concerned with proapoptotic properties of chimera peptides which incorporate sequences of inhibitors of cyclin kinases p161NK4a and p21CIP/WAF1 as well as internalized sequences (Antp and tat). Sequences of the p16 type appeared to be more cytotoxic than the p21 one. Cytotoxic effect proved dependent on orientation with respect to the C or N terminal point of a polypeptide chain rather than on chimera sequence extent. Although p16 endogenous synthesis did not influence chimera peptide levels, apoptosis did not take place in certain cellular lines. Due to the rather unsophisticated nature of such synthesis, it might be used in designing individually-tailored chemotherapeutic drugs.
Subject(s)
Antennapedia Homeodomain Protein/metabolism , Apoptosis , Chimera , Cyclin-Dependent Kinase Inhibitor p16/pharmacology , Cyclin-Dependent Kinase Inhibitor p21/pharmacology , Gene Products, tat/metabolism , Amino Acid Sequence , Apoptosis/drug effects , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Cyclin-Dependent Kinase Inhibitor p21/genetics , Gene Expression Regulation, Neoplastic , Genes, p16 , Genes, p53 , Humans , Jurkat Cells , Molecular Sequence Data , Peptides/pharmacologyABSTRACT
Cluster and discriminant methods were used for analysis of the time course of 12 routine biochemical characteristics of murine serum after tumor transplantation. Mathematical methods helped single out groups of animals with the same prognosis. The methods were tried in clinical studies.
