BACKGROUND/AIM: Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years. PATIENTS AND METHODS: The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis. RESULTS: Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020. CONCLUSION: As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.

• MeSH
• adenokarcinom plic * farmakoterapie   genetika   MeSH
• erbB receptory genetika   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * farmakoterapie   genetika   patologie   MeSH
• protoonkogenní proteiny genetika   MeSH
• tyrosinkinasové receptory genetika   MeSH
• tyrosinkinasy genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Bone regeneration after injury or after surgical bone removal due to disease is a serious medical challenge. A variety of materials are being tested to replace a missing bone or tooth. Regeneration requires cells capable of proliferation and differentiation in bone tissue. Although there are many possible human cell types available for use as a model for each phase of this process, no cell type is ideal for each phase. Osteosarcoma cells are preferred for initial adhesion assays due to their easy cultivation and fast proliferation, but they are not suitable for subsequent differentiation testing due to their cancer origin and genetic differences from normal bone tissue. Mesenchymal stem cells are more suitable for biocompatibility testing, because they mimic natural conditions in healthy bone, but they proliferate more slowly, soon undergo senescence, and some subpopulations may exhibit weak osteodifferentiation. Primary human osteoblasts provide relevant results in evaluating the effect of biomaterials on cellular activity; however, their resources are limited for the same reasons, like for mesenchymal stem cells. This review article provides an overview of cell models for biocompatibility testing of materials used in bone tissue research.

• MeSH
• biokompatibilní materiály farmakologie   MeSH
• buněčná diferenciace MeSH
• kosti a kostní tkáň * MeSH
• kultivované buňky MeSH
• lidé MeSH
• osteoblasty MeSH
• osteogeneze MeSH
• proliferace buněk MeSH
• tkáňové inženýrství * metody   MeSH
• tkáňové podpůrné struktury MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The concept of liquid biopsy as an analysis tool for non-solid tissue carried out for the purpose of providing information about solid tumors was introduced approximately 20 years ago. Additional to the detection of circulating tumor cells (CTCs), the liquid biopsy approach quickly included the analysis of circulating tumor DNA (ctDNA) and other tumor-derived markers such as circulating cell-free RNA or extracellular vesicles. Liquid biopsy is a non-invasive technique for detecting multiple cancer-associated biomarkers that is easy to obtain and can reflect the characteristics of the entire tumor mass. Currently, ctDNA is the key component of the liquid biopsy approach from the point of view of the prognosis assessment, prediction, and monitoring of the treatment of non-small-cell lung cancer (NSCLC) patients. ctDNA in NSCLC patients carries variants or rearrangements that drive carcinogenesis, such as those in EGFR, KRAS, ALK, or ROS1. Due to advances in pharmacology, these variants are the subject of targeted therapy. Therefore, the detection of these variants has gained attention in clinical medicine. Recently, methods based on qPCR (ddPCR, BEAMing) and next-generation sequencing (NGS) are the most effective approaches for ctDNA analysis. This review addresses various aspects of the use of liquid biopsy with an emphasis on ctDNA as a biomarker in NSCLC patients.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND/AIM: The treatment of advanced clear cell renal cell carcinoma (ccRCC) is based on stratification of patients according to prognosis (favorable, intermediate, and poor). The aim of the study was to improve prognostication by biomarkers involved in angiogenesis. PATIENTS AND METHODS: The study group consisted of 20 patients who underwent surgery for ccRCC. Gene expression analysis was peformed on a set of matched (primary tumor, metastasis, n=20+20) FFPE tissue samples. An additional analysis was done on expression data of 606 patients obtained from the TCGA Kidney Clear Cell Carcinoma (KIRC) database. Quantitative estimation of mRNA of selected genes (TaqMan human Angiogenesis Array, 97 genes) was performed by a real-time RT-PCR method with TaqMan® arrays. RESULTS: Using the Cox regression model, 4 genes (PDGFB, FGF4, EPHB2 and BAI1) were identified whose expression was related to progression-free interval (PFI). Further analysis using the Kaplan Meier method conclusively revealed the relationship of BAI1 expression to prognosis (both datasets). Patients with higher BAI1 expression had significantly shorter PFI and overall survival. CONCLUSION: We showed that tumor tissue BAI1 expression level is a prognostic marker in ccRCC. Therefore, this gene might be involved in a prognostic panel to improve scoring systems on which the management of metastatic ccRCC patients is based.

• MeSH
• analýza přežití MeSH
• angiogenní proteiny genetika   MeSH
• karcinom z renálních buněk genetika   mortalita   chirurgie   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory ledvin genetika   mortalita   chirurgie   MeSH
• prognóza MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• regresní analýza MeSH
• regulace genové exprese u nádorů MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese metody   MeSH
• upregulace * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Bone tissue engineering tries to simulate natural behavior of hard tissues. This study aimed to produce scaffolds based on polyvinyl alcohol (PVA) and hyaluronic acid (HA) with hydroxyapatite (HAp) incorporated in two different ways, by in situ synthesis and physical mixing of pre-prepared HAp. In situ synthesis resulted in calcium deficient form of HAp with lower crystallinity. The proliferation of human osteoblast-like cells MG-63 proved to be better in the scaffolds with in situ synthesized HAp compared to those with physically mixed pre-prepared HAp. For scaffolds with PVA/HA/HAp ratio 3:1:2, there was significantly higher initial adhesion (p = 0.0440), as well as the proliferation in the following days (p < 0.001). It seemed to be advantageous improve the properties of the scaffold by in situ synthesizing of HAp directly in the organic matrix.

• MeSH
• biokompatibilní materiály chemie   MeSH
• buněčná adheze MeSH
• hemolýza MeSH
• hydrogely chemie   MeSH
• hydroxyapatit chemie   MeSH
• kyselina hyaluronová chemie   MeSH
• lidé MeSH
• osteoblasty cytologie   MeSH
• polyvinylalkohol chemie   MeSH
• proliferace buněk MeSH
• testování materiálů MeSH
• tkáňové inženýrství MeSH
• tkáňové podpůrné struktury chemie   MeSH
• viabilita buněk MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The aim of the study was to compare the prognostic significance of lymph node status of patients with lung cancer analyzed by three different methods: hematoxylin and eosin (H&E), immunohistochemistry of cytokeratin 19 (IHC CK19), and One-Step Nucleic Acid Amplification (OSNA). The clinical relevance of the results was evaluated based on relation to prognosis; the disease-free interval (DFI) and overall survival (OS) were analyzed. During radical surgical treatment, a total of 1426 lymph nodes were obtained from 100 patients, creating 472 groups of nodes (4-5 groups per patient) and examined by H&E, IHC CK19 and OSNA. The median follow-up was 44 months. Concordant results on the lymph node status of the H&E, IHC CK19 and OSNA examinations were reported in 78% of patients. We recorded shorter OS in patients with positive results provided by both OSNA and H&E. The study demonstrated a higher percentage of detected micrometastases in lymph nodes by the OSNA method. However, the higher sensitivity of the OSNA, with the cut-off value 250 copies of mRNA of CK19/μL, resulted in a lower association of OSNA positivity with progress of the disease compared to H&E. Increasing the cut-off to 615 copies resulted in an increase in concordance between the OSNA and H&E, which means that the higher cut-off is more relevant in the case of lung tumors.

• MeSH
• imunohistochemie metody   MeSH
• keratin-19 genetika   MeSH
• lidé MeSH
• lymfatické metastázy * MeSH
• lymfatické uzliny patologie   MeSH
• metastázy nádorů MeSH
• nádorové biomarkery genetika   MeSH
• nádory plic diagnóza   patologie   chirurgie   MeSH
• následné studie MeSH
• přežití po terapii bez příznaků nemoci MeSH
• prognóza MeSH
• prospektivní studie MeSH
• staging nádorů MeSH
• techniky amplifikace nukleových kyselin metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

This study aimed to develop polyvinyl alcohol (PVA) -based scaffold enriched with hyaluronic acid (HA) and hydroxyapatite (HAp) using physical crosslinking by freezing-thawing method. We accomplished biological evaluation of scaffolds, swelling degree, bioactivity assessment, and hemolytic test. The results showed that all types of scaffolds should be safe for use in the human body. The culturing of human osteoblast-like cells MG-63 and their proliferation showed better adhesion of cells due to the presence of HA and confirmed better proliferation depending on the amount of HAp. This paper gives the optimal composition of the scaffold and the optimal amount of the particular components of the scaffold. Based on our results we concluded that the best PVA/HA/HAp combination is in the ratio 3:1:2.

• MeSH
• biokompatibilní materiály metabolismus   farmakologie   MeSH
• buněčná adheze účinky léků   MeSH
• hydrogely chemie   MeSH
• hydroxyapatit metabolismus   farmakologie   MeSH
• kyselina hyaluronová metabolismus   farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• osteoblasty metabolismus   MeSH
• polyvinylalkohol metabolismus   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• testování materiálů metody   MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: Utilisation of the one-step nucleic acid amplification (OSNA) molecular biology method for the detection of the metastatic involvement of sentinel lymph nodes (SLNs) in endometrial cancer (EC) patients. A comparison with histopathological ultrastaging and a description of the clinical consequences. METHODS: Surgically treated EC patients underwent detection of SLNs. Nodes greater than 5 mm were cut into sections 2-mm thick parallel to the short axis of the node. Odd sections were examined according to the OSNA method, while even ones according to an appropriate ultrastaging protocol. Nodes less than or equal to 5 mm were cut into halves along the longitudinal axis with one half examined according to the OSNA method and the other half by ultrastaging. RESULTS: Fifty-eight patients were included and 135 SLNs were acquired. Both ultrastaging and OSNA agreed on 116 results. According to the OSNA method, 20.69% more patients were classified into International Federation of Gynecology and Obstetrics (FIGO) stage III. When comparing the results of the OSNA method to the conclusions of ultrastaging as a reference method, sensitivity of 90.9%, specificity of 85.5% and concordance of 85.9% were attained. CONCLUSIONS: The results of the OSNA method showed a higher frequency of detection of micrometastases and included 20.69% more patients into FIGO stage III.

• MeSH
• adenokarcinom z jasných buněk genetika   sekundární   chirurgie   MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• dospělí MeSH
• keratin-19 genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• mikrometastázy MeSH
• míra přežití MeSH
• nádorové biomarkery genetika   MeSH
• nádory endometria genetika   patologie   chirurgie   MeSH
• následné studie MeSH
• nukleové kyseliny analýza   genetika   MeSH
• peroperační doba MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sentinelová uzlina patologie   chirurgie   MeSH
• serózní cystadenokarcinom genetika   sekundární   chirurgie   MeSH
• techniky amplifikace nukleových kyselin metody   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
• srovnávací studie MeSH

Colorectal cancer (CRC) ranks among the most common cancers worldwide. Surgical removal remains the best strategy for treatment of resectable tumors. An important part of caring for patients after surgery is monitoring for early detection of a possible relapse of the disease. Efforts are being made to improve the sensitivity and specificity of routinely used carcinoembryonic antigen (CEA) with the use of additional biomarkers such as microRNAs. The aim of our study was to evaluate the prognostic potential of microRNAs and their use as markers of disease recurrence. The quantitative estimation of CEA, CA19-9, and 22 selected microRNAs (TaqMan Advanced miRNA Assays) was performed in 85 paired (preoperative and postoperative) blood plasma samples of CRC patients and in samples taken during the follow-up period. We have revealed a statistically significant decrease in plasma levels for miR-20a, miR-23a, miR-210, and miR-223a (p = 0.0093, p = 0.0013, p = 0.0392, and p = 0.0214, respectively) after surgical removal of the tumor tissue. A statistically significant relation to prognosis (overall survival; OS) was recorded for preoperative plasma levels of miR-20a, miR-21, and miR-23a (p = 0.0236, p = 0.0316, and p =0.0271, respectively) in a subgroup of patients who underwent palliative surgery. The best discrimination between patients with favorable and unfavorable outcomes was achieved by a combination of CEA, CA19-9 with miR-21, miR-20a, and miR-23a (p < 0.0001). The use of these microRNAs for early disease recurrence detection was affected by a low specificity in comparison with CEA and CA19-9. CEA and CA19-9 had high specificity but low sensitivity. Our results show the benefit of combining currently used standard biomarkers and microRNAs for precise prognosis estimation.

• Publikační typ
• časopisecké články MeSH

Modelové testy z oblasti chemie pro rok 2019. Určeno pro uchazeče o studium všeobecného a zubního lékařství.

• MeSH
• chemie výchova   MeSH
• přijímací zkouška na vysokou školu MeSH
• studium lékařství MeSH
• univerzity MeSH
• Publikační typ
• učebnice MeSH

• Konspekt
• Chemie. Mineralogické vědy
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• chemie, klinická chemie
• NLK Publikační typ
• testy