RESUMEN
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.
Asunto(s)
Apoptosis/efectos de la radiación , Rayos gamma , Linfocitos/efectos de la radiación , Línea Celular Tumoral , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Células Jurkat , Linfocitos/patología , Necrosis/patología , Cultivo Primario de CélulasRESUMEN
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.
Asunto(s)
Antígeno Carcinoembrionario/inmunología , Citotoxicidad Inmunológica , Receptores de Antígenos de Linfocitos T/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Supervivencia Celular , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Inmunoterapia , Neoplasias/inmunología , Neoplasias/terapia , Receptores de Antígenos de Linfocitos T/genética , Proteínas Recombinantes de Fusión/genética , TransfecciónRESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/farmacología , Neoplasias/tratamiento farmacológico , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/uso terapéutico , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias/metabolismo , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
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.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Ciclinas/antagonistas & inhibidores , Citostáticos/metabolismo , Factor de Transcripción E2F1/metabolismo , Fragmentos de Péptidos/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Células Cultivadas , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Factor de Transcripción E2F1/genética , Humanos , Fragmentos de Péptidos/genética , Proteínas Recombinantes de Fusión/genéticaRESUMEN
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.
Asunto(s)
Proteína con Homeodominio Antennapedia/metabolismo , Apoptosis , Quimera , Inhibidor p16 de la Quinasa Dependiente de Ciclina/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/farmacología , Productos del Gen tat/metabolismo , Secuencia de Aminoácidos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Genes p16 , Genes p53 , Humanos , Células Jurkat , Datos de Secuencia Molecular , Péptidos/farmacologíaRESUMEN
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.