- MeSH
- chlupatý jazyk * diagnóza etiologie terapie MeSH
- dysbióza etiologie komplikace terapie MeSH
- hospitalizace MeSH
- kojenec MeSH
- lidé MeSH
- probiotika terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Vydání první 278 stran : ilustrace ; 21 cm
Publikace se zaměřuje na terapii bolestí zad a psychologické faktory, které je způsobují. Zaměřuje se na syndrom zánětu svalů z napětí. Určeno odborné i široké veřejnosti.
- MeSH
- bolesti zad psychologie terapie MeSH
- management bolesti MeSH
- péče o sebe MeSH
- psychosomatické lékařství MeSH
- psychosomatické poruchy terapie MeSH
- záda MeSH
- Publikační typ
- monografie MeSH
- populární práce MeSH
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- ortopedie
- psychologie, klinická psychologie
In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile.
- MeSH
- antigeny nádorové analýza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádorové buněčné linie MeSH
- nádorové buňky kultivované MeSH
- nádory glandulární a epitelové imunologie MeSH
- nádory vaječníků imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transkriptom * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
PURPOSE: We conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms. EXPERIMENTAL DESIGN: Twenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis. RESULTS: No serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13-0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17-0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS. CONCLUSIONS: In patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.
- MeSH
- adenokarcinom imunologie mortalita sekundární terapie MeSH
- adjuvantní chemoterapie MeSH
- antitumorózní látky alkylující aplikace a dávkování MeSH
- časové faktory MeSH
- cyklofosfamid aplikace a dávkování MeSH
- dendritické buňky imunologie transplantace MeSH
- imunoterapie škodlivé účinky metody mortalita MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- metronomické podávání léků MeSH
- nádory prostaty rezistentní na kastraci farmakoterapie imunologie mortalita patologie MeSH
- nomogramy MeSH
- prednison aplikace a dávkování MeSH
- proporcionální rizikové modely MeSH
- protokoly antitumorózní kombinované chemoterapie aplikace a dávkování škodlivé účinky MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- taxoidy aplikace a dávkování MeSH
- tumor infiltrující lymfocyty imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- klinické zkoušky, fáze II MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Dendritic cells (DCs) play an important role in pathogenesis of autoimmunity, including type 1 diabetes (T1D). In this study, we investigated DC subpopulations and their responses to TLR stimulation in T1D patients and their relatives. METHODS: We analyzed the frequency of myeloid (mDCs) and plasmacytoid DCs (pDCs) in 97 T1D patients (69 onset, 28 long-term), 67 first-degree relatives, and 64 controls. We additionally tested the IFN-alpha production by pDCs upon stimulation with TLR 7, 8 and 9 agonists. RESULTS: A lower number of mDCs and pDCs were found in T1D patients and their relatives. Of all the tested TLR ligands, only stimulation with CpG 2216 induced IFN-alpha production that was the highest in T1D relatives, except of autoantibody-negative relatives bearing the protective haplotypes. CONCLUSION: Our data demonstrate disturbances in DC number and function expressed most significantly in T1D relatives and point to a potential role of TLR9-induced IFN-alpha production in T1D development.
- MeSH
- dendritické buňky imunologie metabolismus MeSH
- diabetes mellitus 1. typu imunologie metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- interferon alfa biosyntéza krev MeSH
- leukocyty mononukleární účinky léků metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- mladiství MeSH
- mladý dospělý MeSH
- oligodeoxyribonukleotidy farmakologie MeSH
- počet buněk MeSH
- předškolní dítě MeSH
- rodina MeSH
- toll-like receptor 9 metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. We studied the immune cells that infiltrated the tumor tissues of ovarian cancer patients at different stages of disease. The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (Stages III-IV), we detected a dominant population of Helios(+) activated regulatory T cells (Tregs) along with high numbers of monocytes/macrophages and myeloid dendritic cells (mDCs). Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, monocytes/macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNγ. Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
- MeSH
- buňky - růstové procesy imunologie MeSH
- buňky Th17 imunologie metabolismus MeSH
- CD8-pozitivní T-lymfocyty imunologie metabolismus patologie MeSH
- chemokin CCL22 imunologie metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- dospělí MeSH
- interferon gama imunologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy imunologie metabolismus MeSH
- monocyty imunologie metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí imunologie MeSH
- nádory vaječníků imunologie metabolismus patologie MeSH
- progrese nemoci MeSH
- receptory CCR4 imunologie metabolismus MeSH
- regulační T-lymfocyty imunologie metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tumor infiltrující lymfocyty imunologie metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
