Glioblastoma is the commonest primary malignant brain tumor, with a very poor prognosis and short overall survival. It is characterized by its high intra- and intertumoral heterogeneity, in terms of both the level of single-nucleotide variants, copy number alterations, and aneuploidy. Therefore, routine diagnosis can be challenging in some cases. We present a complicated case of glioblastoma, which was characterized with five cytogenomic methods: interphase fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, comparative genomic hybridization array and single-nucleotide polymorphism, targeted gene panel, and whole-genome sequencing. These cytogenomic methods revealed classical findings associated with glioblastoma, such as a lack of IDH and TERT mutations, gain of chromosome 7, and loss of chromosome 10. At least three pathological clones were identified, including one with whole-genome duplication, and one with loss of 1p and suspected loss of 19q. Deletion and mutation of the TP53 gene were detected with numerous breakends on 17p and 20q. Based on these findings, we recommend a combined approach to the diagnosis of glioblastoma involving the detection of copy number alterations, mutations, and aneuploidy. The choice of the best combination of methods is based on cost, time required, staff expertise, and laboratory equipment. This integrated strategy could contribute directly to tangible improvements in the diagnosis, prognosis, and prediction of the therapeutic responses of patients with brain tumors.

• Klíčová slova
• I-FISH, MLPA, WGS, aCGH/SNP, cytogenomics, diagnostics, gene panel,
• MeSH
• glioblastom * genetika   patologie   diagnóza   MeSH
• hybridizace in situ fluorescenční metody   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery genetika   MeSH
• nádory mozku * genetika   patologie   diagnóza   MeSH
• prognóza MeSH
• srovnávací genomová hybridizace metody   MeSH
• variabilita počtu kopií segmentů DNA MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• nádorové biomarkery MeSH

Amyloidosis is a rare metabolic disorder primarily brought on by misfolding of an autologous protein, which causes its local or systemic deposition in an aberrant fibrillar form. It is quite rare for pulmonary tissue to be impacted by amyloidosis; of the three forms it can take when involving pulmonary tissue, nodular pulmonary amyloidosis is the most uncommon. Nodular pulmonary amyloidosis rarely induces clinical symptoms, and most often, it is discovered accidentally during an autopsy or via imaging techniques. Only one case of nodular pulmonary amyloidosis, which manifested as a spontaneous pneumothorax, was found in the literature. In terms of more precise subtyping, nodular amyloidosis is typically AL or mixed AL/AH type. No publications on AH-dominant type of nodular amyloidosis were found in the literature. We present a case of an 81 years-old male with nodular pulmonary AH-dominant type amyloidosis who presented with spontaneous pneumothorax. For a deeper understanding of the subject, this study also provides a review of the literature on cases with nodular pulmonary amyloidosis in relation to precise amyloid fibril subtyping. Since it is often a difficult process, accurate amyloid type identification is rarely accomplished. However, this information is very helpful for identifying the underlying disease process (if any) and outlining the subsequent diagnostic and treatment steps. Even so, it is crucial to be aware of this unit and make sure it is taken into consideration when making a differential diagnosis of pulmonary lesions.

• Klíčová slova
• AH amyloidosis, amyloidoma, amyloidosis, nodular pulmonary amyloidosis, pneumothorax,
• MeSH
• amyloidóza * komplikace   diagnóza   patologie   MeSH
• familiární amyloidóza MeSH
• genetická onemocnění kůže MeSH
• lidé MeSH
• plíce diagnostické zobrazování   patologie   MeSH
• plicní nemoci * komplikace   diagnóza   patologie   MeSH
• pneumotorax * diagnóza   etiologie   MeSH
• senioři nad 80 let MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

Lung cancer is one of the leading causes of cancer-related deaths worldwide, with small cell lung cancer (SCLC) having the worst prognosis. SCLC is diagnosed late in the disease's progression, limiting treatment options. The most common treatment for SCLC is chemotherapy. As the disease progresses, immunotherapy, most commonly checkpoint inhibitor medication, becomes more important. Efforts should be made in the development of immunotherapy to map specific biomarkers, which play a role in properly assigning a type of immunotherapy to the right cohort of patients, where the benefits outweigh any risks or adverse effects. The objective of this review was to provide a thorough assessment of current knowledge about the nature of the tumor process and treatment options for small cell lung cancer, with a focus on predictive biomarkers. According to the information obtained, the greatest potential, which has already been directly demonstrated in some studies, has characteristics such as tumor microenvironment composition, tumor mutation burden, and molecular subtyping of SCLC. Several other aspects appear to be promising, but more research, particularly prospective studies on a larger number of probands, is required. However, it is clear that this field of study will continue to expand, as developing a reliable method to predict immunotherapy response is a very appealing goal of current medicine and research in the field of targeted cancer therapy.

• Klíčová slova
• PD-L1 expression, molecular subtyping, mutational burden, small cell lung cancer, tumor microenvironment,
• MeSH
• imunoterapie metody   MeSH
• lidé MeSH
• malobuněčný karcinom plic * genetika   MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové mikroprostředí MeSH
• nádory plic * genetika   MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH

Tisagenlecleucel (tisa-cel) is a CD19-specific CAR-T cell product approved for the treatment of relapsed/refractory (r/r) DLBCL or B-ALL. We have followed a group of patients diagnosed with childhood B-ALL (n = 5), adult B-ALL (n = 2), and DLBCL (n = 25) who were treated with tisa-cel under non-clinical trial conditions. The goal was to determine how the intensive pretreatment of patients affects the produced CAR-T cells, their in vivo expansion, and the outcome of the therapy. Multiparametric flow cytometry was used to analyze the material used for manufacturing CAR-T cells (apheresis), the CAR-T cell product itself, and blood samples obtained at three timepoints after administration. We present the analysis of memory phenotype of CD4/CD8 CAR-T lymphocytes (CD45RA, CD62L, CD27, CD28) and the expression of inhibitory receptors (PD-1, TIGIT). In addition, we show its relation to the patients' clinical characteristics, such as tumor burden and sensitivity to prior therapies. Patients who responded to therapy had a higher percentage of CD8+CD45RA+CD27+ T cells in the apheresis, although not in the produced CAR-Ts. Patients with primary refractory aggressive B-cell lymphomas had the poorest outcomes which was characterized by undetectable CAR-T cell expansion in vivo. No clear correlation of the outcome with the immunophenotypes of CAR-Ts was observed. Our results suggest that an important parameter predicting therapy efficacy is CAR-Ts' level of expansion in vivo but not the immunophenotype. After CAR-T cells' administration, measurements at several timepoints accurately detect their proliferation intensity in vivo. The outcome of CAR-T cell therapy largely depends on biological characteristics of the tumors rather than on the immunophenotype of produced CAR-Ts.

• Klíčová slova
• B-cell lymphoma and leukemia, CAR-T cells, Kymriah, immunotherapy, tisagenlecleucel,
• MeSH
• B-buněčný lymfom * MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• difúzní velkobuněčný B-lymfom * patologie   MeSH
• imunoterapie adoptivní metody   MeSH
• lidé MeSH
• průtoková cytometrie MeSH
• receptory antigenů T-buněk metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory antigenů T-buněk MeSH
• tisagenlecleucel MeSH Prohlížeč

• Klíčová slova
• circulating tumor cells, ctDNA, exosomes, liquid biopsy, monitoring,
• MeSH
• cirkulující nádorová DNA * MeSH
• lidé MeSH
• tekutá biopsie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• úvodníky MeSH
• Názvy látek
• cirkulující nádorová DNA * MeSH

Signal transducer and activator of transcription 3 (Stat3) is responsible for many aspects of normal development and contributes to the development and progression of cancer through regulating epithelial cell identity and cancer stem cells. In breast cancer, Stat3 is associated with triple-negative breast cancers (TNBC) and its function has been related to the activation of p63, itself a marker of basal-like TNBC and a master regulator of stem cell activities. Stat3 activation is controlled by dual phosphorylation at tyrosine 705 (pTyr705) and serine 727 (pSer727), although it is unclear whether these have equivalent effects, and whether they are related or independent events. To address these issues, we investigated Stat3 phosphorylation at the two sites by immunohistochemistry in 173 patients with TNBC. Stat3 phosphorylation was assessed by automated quantitative measurements of digitized scanned images and classified into four categories based on histoscore. The results were analyzed for associations with multiple markers of tumor phenotype, proliferation, BRCA status, and clinicopathological characteristics. We show that the levels of pTyr705- and pSer727-Stat3 were independent in 34% of tumors. High pTyr705-Stat3 levels were associated with the luminal differentiation markers ERβ/AR and MUC1, whereas tumors with high levels of pSer727-Stat3 were more likely to be positive for the basal marker CK5/6, but were independent of p63 and were EGFR negative. Combined high pSer727- and low Tyr705-Stat3 phosphorylation associated with basal-like cancer. Although high Stat3 phosphorylation levels were associated with less aggressive tumor characteristics, they did not associate with improved survival, indicating that Stat3 phosphorylation is an unfavorable indicator for tumors with an otherwise good prognosis according to clinicopathological characteristics. These findings also show that pTyr705-Stat3 and pSer727-Stat3 associate with specific breast tumor phenotypes, implying that they exert distinct functional activities in breast cancer.

• Klíčová slova
• Stat3 serine phosphorylation, Stat3 tyrosine phosphorylation, clinicopathological characteristics, triple-negative breast cancer, tumor cell phenotypes,
• MeSH
• fenotyp MeSH
• fosforylace MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• serin genetika   MeSH
• transkripční faktor STAT3 metabolismus   MeSH
• triple-negativní karcinom prsu * patologie   MeSH
• tyrosin genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• serin MeSH
• STAT3 protein, human MeSH Prohlížeč
• transkripční faktor STAT3 MeSH
• tyrosin MeSH

Colorectal cancer (CRC) is one of the most common cancers worldwide. The patient's prognosis largely depends on the tumor stage at diagnosis. The pathological TNM Classification of Malignant Tumors (pTNM) staging of surgically resected cancers represents the main prognostic factor and guidance for decision-making in CRC patients. However, this approach alone is insufficient as a prognostic predictor because clinical outcomes in patients at the same histological tumor stage can still differ. Recently, significant progress in the treatment of CRC has been made due to improvements in both chemotherapy and surgical management. Immunotherapy-based approaches are one of the most rapidly developing areas of tumor therapy. This review summarizes the current knowledge about the tumor microenvironment (TME), immune response and its interactions with CRC development, immunotherapy and prognosis.

• Klíčová slova
• colorectal cancer, consensus molecular subtypes, immune cells, immunoscore, tumor microenvironment, tumorigenesis,
• MeSH
• imunita MeSH
• imunoterapie MeSH
• kolorektální nádory * patologie   MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Background: Observation of anticancer therapy effect by monitoring of minimal residual disease (MRD) is becoming an important tool in management of non-small cell lung cancer (NSCLC). The approach is based on periodic detection and quantification of tumor-specific somatic DNA mutation in circulating tumor DNA (ctDNA) extracted from patient plasma. For such repetitive testing, complex liquid-biopsy techniques relying on ultra-deep NGS sequencing are impractical. There are other, cost-effective, methods for ctDNA analysis, typically based on quantitative PCR or digital PCR, which are applicable for detecting specific individual mutations in hotspots. While such methods are routinely used in NSCLC therapy prediction, however, extension to cover broader spectrum of mutations (e.g., in tumor suppressor genes) is required for universal longitudinal MRD monitoring. Methods: For a set of tissue samples from 81 NSCLC patients we have applied a denaturing capillary electrophoresis (DCE) for initial detection of somatic mutations within 8 predesigned PCR amplicons covering oncogenes and tumor suppressor genes. Mutation-negative samples were then subjected to a large panel NGS sequencing. For each patient mutation found in tissue was then traced over time in ctDNA by DCE. Results: In total we have detected a somatic mutation in tissue of 63 patients. For those we have then prospectively analyzed ctDNA from collected plasma samples over a period of up to 2 years. The dynamics of ctDNA during the initial chemotherapy therapy cycles as well as in the long-term follow-up matched the clinically observed response. Conclusion: Detection and quantification of tumor-specific mutations in ctDNA represents a viable complement to MRD monitoring during therapy of NSCLC patients. The presented approach relying on initial tissue mutation detection by DCE combined with NGS and a subsequent ctDNA mutation testing by DCE only represents a cost-effective approach for its routine implementation.

• Klíčová slova
• KRAS mutations, NSCLC, TP53 mutations, capillary electrophoresis, ctDNA, liquid biopsy, minimal residual disease,
• MeSH
• cirkulující nádorová DNA * genetika   MeSH
• DNA nádorová genetika   MeSH
• elektroforéza kapilární MeSH
• lidé MeSH
• mutace genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory plic * farmakoterapie   MeSH
• nemalobuněčný karcinom plic * genetika   terapie   MeSH
• reziduální nádor MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cirkulující nádorová DNA * MeSH
• DNA nádorová MeSH
• nádorové biomarkery MeSH

Replicative senescence is irreversible cell proliferation arrest for somatic cells which can be circumvented in cancers. Cellular senescence is a process, which may play two opposite roles. On the one hand, this is a natural protection of somatic cells against unlimited proliferation and malignant transformation. On the other hand, cellular secretion caused by senescence can stimulate inflammation and proliferation of adjacent cells that may promote malignancy. The main genes controlling the senescence pathways are also well known as tumor suppressors. Almost 140 genes regulate both cellular senescence and cancer pathways. About two thirds of these genes (64%) are regulated by microRNAs. Senescence-associated miRNAs can stimulate cancer progression or act as tumor suppressors. Here we review the role playing by senescence-associated miRNAs in development, diagnostics and treatment of pancreatic cancer.

• Klíčová slova
• cellular senescence, oncogene, pancreatic ductal adenocarcinoma, senescence bypass, senescence-associated miRNA, tumor suppressor,
• MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• proliferace buněk genetika   MeSH
• stárnutí buněk genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA * MeSH

Small cell carcinoma of hypercalcemic type (SCCOHT) is a rare gynaecological neoplasm, originating mostly in the ovaries. Cervical origin of this very aggressive malignancy with unknown histogenesis is an extremely rare condition, without published management recommendations. Alterations in SMARCA4 gene are supposed to play the major role in SCCOHT oncogenesis and their identification is crucial for the diagnosis. Adequate genetic counselling of the patients and their families seems to be of great importance. Optimal management and treatment approaches are not known yet but may extremely influence the prognosis of young female patients that suffer from this very resistant disease. Nowadays, a translational research seems to be the key for the further diagnostic and treatment strategies of SCCOHT. The purpose of the case report is to provide practical information and useful recommendations on the diagnosis, management, and treatment of SMARCA4-deficient carcinoma of the uterine cervix resembling SCCOHT.

• Klíčová slova
• case report, cervical cancer, diagnostic biomarker, gynecological cancer, high-risk, personalized treatment, predictive marker,
• MeSH
• DNA-helikasy nedostatek   genetika   MeSH
• fatální výsledek MeSH
• hyperkalcemie diagnóza   genetika   metabolismus   terapie   MeSH
• jaderné proteiny nedostatek   genetika   MeSH
• lidé MeSH
• malobuněčný karcinom diagnóza   genetika   metabolismus   terapie   MeSH
• mladiství MeSH
• mutace MeSH
• nádorové biomarkery nedostatek   genetika   MeSH
• nádory děložního čípku diagnóza   genetika   metabolismus   terapie   MeSH
• transkripční faktory nedostatek   genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• DNA-helikasy MeSH
• jaderné proteiny MeSH
• nádorové biomarkery MeSH
• SMARCA4 protein, human MeSH Prohlížeč
• transkripční faktory MeSH