Kvardová, K*
Dotaz
Zobrazit nápovědu
- MeSH
- dějiny 16. století MeSH
- dějiny 18. století MeSH
- dějiny 19. století MeSH
- dějiny lékařství * MeSH
- rukopisy jako téma * dějiny MeSH
- rukopisy lékařské jako téma * dějiny MeSH
- tradiční lékařství dějiny MeSH
- Check Tag
- dějiny 16. století MeSH
- dějiny 18. století MeSH
- dějiny 19. století MeSH
- Publikační typ
- historické články MeSH
In this study, we characterized the effects of LA-12 on tumor cell lines possessing wild type p53 and on p53-deficient/mutant cell lines and the results were compared to those obtained using cisplatin. We have determined changes of p53 levels, of its transcriptional activity, of its posttranscriptional modifications and the effect of the treatment on the cell cycle, on the induction of apoptosis and on gene expression. LA-12 induces weak accumulation of both transcriptionally active p53 tumor suppressor and of p21(WAF1/CIP1) protein. LA-12 and cisplatin also significantly differ in their effects on apoptosis and cell cycle and on gene expression spectra in studied cell lines. LA-12 induces higher apoptosis levels in comparison with those induced by cisplatin, especially in p53-deficient H1299 cells and in MCF-7DD cells with transcriptionally inactive p53. We suggest that LA-12-mediated apoptosis is not fully dependent on p53. This confirms the therapeutic potential of LA-12 as a more potent cytostatic agent for both tumor cells expressing wild type p53 and for p53-deficient or mutant cells.
- MeSH
- amantadin analogy a deriváty farmakologie MeSH
- apoptóza účinky léků MeSH
- buněčný cyklus účinky léků MeSH
- cisplatina farmakologie MeSH
- geny p53 MeSH
- inhibitor p21 cyklin-dependentní kinasy metabolismus MeSH
- lidé MeSH
- mutace MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 genetika metabolismus MeSH
- organoplatinové sloučeniny farmakologie MeSH
- proteiny regulující apoptózu metabolismus MeSH
- protinádorové látky farmakologie MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Immunotherapy emerges as a fundamental approach in cancer treatment. Up to date, the efficacy of numerous different immunotherapies has been evaluated. The use of microorganisms or their parts for immune cell activation, referred to as Pathogen-Associated Molecular Patterns (PAMPs), represents highly promising concept. The therapeutic effect of PAMPs can be further amplified by suitable combination of different types of PAMPs such as Toll like receptor (TLR) agonists and phagocytosis activating ligands. Previously, we used the combination of phagocytosis activating ligand (mannan) and mixture of TLR agonists (resiquimod (R-848), poly(I:C), inactivated Listeria monocytogenes) for successful treatment of melanoma in murine B16-F10 model. In the present study, we optimized the composition and timing of previously used mixture. Therapeutic mixture based on well-defined chemical compounds consisted of mannan anchoring to tumor cell surface by biocompatible anchor for membranes (BAM) and TLR agonists resiquimod, poly(I:C), and lipoteichoic acid (LTA). The optimization resulted in (1) eradication of advanced stage progressive melanoma in 83% of mice, (2) acquisition of resistance to tumor re-transplantation, and (3) potential anti-metastatic effect. After further investigation of mechanisms, underlying anti-tumor responses, we concluded that both innate and adaptive immunity are activated and involved in these processes. We tested the efficacy of our treatment in Panc02 murine model of aggressive pancreatic tumor as well. Simultaneous application of agonistic anti-CD40 antibody was necessary to achieve effective therapeutic response (80% recovery) in this model. Our results suggest that herein presented immunotherapeutic approach is a promising cancer treatment strategy with the ability to eradicate not only primary tumors but also metastases.
- MeSH
- adenokarcinom imunologie patologie terapie MeSH
- fagocytóza * MeSH
- imidazoly terapeutické užití MeSH
- imunoterapie MeSH
- kyseliny teichoové terapeutické užití MeSH
- lipopolysacharidy terapeutické užití MeSH
- mannany terapeutické užití MeSH
- melanom experimentální imunologie patologie terapie MeSH
- myši inbrední C57BL MeSH
- nádorové buněčné linie MeSH
- nádory slinivky břišní imunologie patologie terapie MeSH
- neutrofily imunologie MeSH
- poly I-C terapeutické užití MeSH
- toll-like receptory agonisté MeSH
- tumor burden účinky léků MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
