Q86538022
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Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
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Cílem projektu je detekovat cirkulující nádorové buňky (CTC) v periferní krvi u pacientů s metastatickým karcinomem prostaty před cytotoxickou léčbou a v jejím průběhu. Detekce bude provedena metodou imunomagnetické separace buněk a izolací RNA z této frakce. Dále proběhne kultivace části detekovaných buněk včetně kultivace v prostředí cytotoxických látek. V další fázi bude hodnocen genetický profil zjištěných buněk (stanovení panelu 24 genů) a obdobný profil také u histologického preparátu primárního tumoru. Výsledky analýz budou vztaženy na klinický průběh onemocnění a budou stanoveny prognostické faktory účinku léčby na pokles CTC a přežití pacientů.; The aim of the project is to detect circulating tumor cells (CTC) in peripheral blood of patients with metastatic prostate cancer before and during the cytotoxic therapy. Detection will be performed by the method of immunomagnetic separation and RNA isolation from this fraction. Then we will perform the cultivation of the detected cells including the cultivation in milieu of cytotoxic agents. In the next stage the genetic profile of the detected cells will be assessed (a panel of 24 genes) and a similar profile will be evaluated also in histological specimen of a primary tumor. Analysis results will be correlated to the clinical course of disease and the prognostic factors of treatment effect on CTC count decline and patients‘ survival will be determined.
- MeSH
- analýza přežití MeSH
- diagnostické techniky molekulární MeSH
- exprese genu MeSH
- imunomagnetická separace MeSH
- individualizovaná medicína MeSH
- nádorové buněčné linie cytologie MeSH
- nádorové cirkulující buňky MeSH
- nádory prostaty rezistentní na kastraci diagnóza MeSH
- prognóza MeSH
- prostatický specifický antigen analýza MeSH
- RNA analýza MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- andrologie
- onkologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
PURPOSE: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. METHODS: In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. RESULTS: Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. CONCLUSION: Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.
- MeSH
- antigeny CD274 MeSH
- biologické markery MeSH
- hemoglobiny terapeutické užití MeSH
- imunofenotypizace MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- nádory plic * MeSH
- nemalobuněčný karcinom plic * MeSH
- nivolumab terapeutické užití MeSH
- prospektivní studie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND AND AIMS: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients. PATIENTS AND METHODS: The groups comprised 44 advanced HER2 BC, 24 CRPC patients and 42 healthy controls. An immunomagnetic separation method followed by PCR and electrophoretic detection (AdnaGen, Germany) were used for CTC determination. Serum marker levels were determined by the ELISAs (R&D System, USA). RESULTS: MMP-2 serum level was significantly higher in HER2 BC patients who developed CNS metastases, especially if there were also bone metastases. CTCs were a negative predictive marker for overall survival in HER2 BC patients. MMP-9 serum level was significantly higher in CRPC patients in whom disease progression occurred. CTC vanished from the blood of most of the CRPC patients (from 88% to 37%) during chemotherapy. CONCLUSION: MMP-2 serum level and CTCs show the potential to predict CNS metastases and overall survival in BC patients. CTCs and MMP-9 serum level could be a promising therapy response marker in CRPC patients.
- MeSH
- dospělí MeSH
- geny erbB-2 MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 krev MeSH
- matrixová metaloproteinasa 9 krev MeSH
- metastázy nádorů * patologie MeSH
- míra přežití MeSH
- nádorové biomarkery krev MeSH
- nádorové cirkulující buňky patologie MeSH
- nádory centrálního nervového systému krev sekundární MeSH
- nádory prostaty rezistentní na kastraci krev patologie MeSH
- nádory prsu krev metabolismus patologie MeSH
- prediktivní hodnota testů MeSH
- progrese nemoci MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování MeSH
- trastuzumab aplikace a dávkování terapeutické užití MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Detection of circulating tumor cells (CTC) in patients with castration-resistant prostate cancer (CRPC) may improve the estimate of chemotherapy response. We evaluated the AdnaTest® system in patients receiving docetaxel. PATIENTS AND METHODS: CTC analysis was carried out in 37 patients by immunomagnetic separation. Correlation between serum prostate-specific antigen (sPSA) change and CTC presence and the influence of each parameter on the overall survival (OS) were evaluated. RESULTS: We detected CTCs in 32 and 16 patients before and after three docetaxel cycles, respectively. The sPSA level correlated with CTC positivity during docetaxel therapy (p=0.0031). The longest OS was in patients negative for CTCs in both samples (p=0.0228). Change in sPSA levels was associated with treatment response (p=0.033). CONCLUSION: We detected CTCs in a considerable number of patients with CRPC. The absolute change of sPSA level correlated with OS. CTC presence during docetaxel therapy was associated with shorter OS.
- MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- nádory prostaty rezistentní na kastraci krev patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prognóza MeSH
- prostatický specifický antigen krev MeSH
- protinádorové látky terapeutické užití MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- taxoidy terapeutické užití 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
- práce podpořená grantem MeSH
INTRODUCTION: Nowadays, on-a-chip capillary electrophoresis is a routine method for the detection of PCR fragments. The Agilent 2100 Bioanalyzer was one of the first commercial devices in this field. Our project was designed to study the characteristics of Agilent DNA 1000 kit in PCR fragment analysis as a part of circulating tumour cell (CTC) detection technique. Despite the common use of this kit a complex analysis of the results from a long-term project is still missing. MATERIALS AND METHODS: A commercially available Agilent DNA 1000 kit was used as a final step in the CTC detection (AdnaTest) for the determination of the presence of PCR fragments generated by Multiplex PCR. Data from 30 prostate cancer patients obtained during two years of research were analyzed to determine the trueness and precision of the PCR fragment size determination. Additional experiments were performed to demonstrate the precision (repeatability, reproducibility) and robustness of PCR fragment concentration determination. RESULTS: The trueness and precision of the size determination was below 3% and 2% respectively. The repeatability of the concentration determination was below 15%. The difference in concentration determination increases when Multiplex-PCR/storage step is added between the two measurements of one sample. CONCLUSIONS: The characteristics established in our study are in concordance with the manufacturer's specifications established for a ladder as a sample. However, the concentration determination may vary depending on chip preparation, sample storage and concentration. The 15% variation of concentration determination repeatability was shown to be partly proportional and can be suppressed by proper normalization.
- MeSH
- aktiny genetika MeSH
- antigeny povrchové genetika MeSH
- DNA nádorová genetika MeSH
- erbB receptory genetika MeSH
- glutamátkarboxypeptidasa II genetika MeSH
- laboratoř na čipu * MeSH
- lidé MeSH
- multiplexová polymerázová řetězová reakce metody MeSH
- nádorové biomarkery genetika MeSH
- nádorové cirkulující buňky metabolismus MeSH
- nádory prostaty rezistentní na kastraci krev genetika MeSH
- prostatický specifický antigen genetika MeSH
- reagenční diagnostické soupravy MeSH
- regulace genové exprese u nádorů * MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
