INTRODUCTION: Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. HYPOTHESIS: Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. AIMS OF THE STUDY AND METHODS: Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. RESULTS: The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. CONCLUSION: This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

• Publikační typ
• časopisecké články MeSH

Hyperthermia along with hydrocortisone (HC) are proven teratogens that can negatively influence embryo development during early pregnancy. Proliferation of cells is one of the main developmental processes during the early embryogenesis. This study was focused on testing the effect of elevated temperature and HC addition on proliferation of cells in in vitro cultures. The V79-4 cell line was treated with HC and cultured in vitro at 37 °C or 39 °C, respectively. To reveal the effect of both factors, the proliferation of cells cultured under different conditions was evaluated using various approaches (colony formation assay, generation of growth curves, computation of doubling times, and mitotic index estimation). Our results indicate that a short-term exposure to elevated temperature slightly stimulates and a long-term exposure suppresses cell proliferation. However, HC (0.1 mg/ml) acts as a stimulator of cell proliferation. Interestingly, the interaction of HC and long-term elevated temperature (39 °C) exposure results in at least partial compensation of the negative impact of elevated temperature by HC addition and in higher proliferation if compared with cells cultured at 39 °C without addition of HC.

• MeSH
• Cricetulus MeSH
• fibroblasty * účinky léků   cytologie   metabolismus   MeSH
• hydrokortison * farmakologie   MeSH
• kultivované buňky MeSH
• proliferace buněk * účinky léků   MeSH
• teplota MeSH
• vysoká teplota MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Introduction: Based on extensive data from oncology research, the use of phytochemicals or plant-based nutraceuticals is considered an innovative tool for cancer management. This research aimed to analyze the oncostatic properties of Salvia officinalis L. [Lamiaceae; Salviae officinalis herba] using animal and in vitro models of breast carcinoma (BC). Methods: The effects of dietary administered S. officinalis in two concentrations (0.1%/SAL 0.1/and 1%/SAL 1/) were assessed in both syngeneic 4T1 mouse and chemically induced rat models of BC. The histopathological and molecular evaluations of rodent carcinoma specimens were performed after the autopsy. Besides, numerous in vitro analyses using two human cancer cell lines were performed. Results and Conclusion: The dominant metabolites found in S. officinalis propylene glycol extract (SPGE) were representatives of phenolics, specifically rosmarinic, protocatechuic, and salicylic acids. Furthermore, the occurrence of triterpenoids ursolic and oleanolic acid was proved in SPGE. In a mouse model, a non-significant tumor volume decrease after S. officinalis treatment was associated with a significant reduction in the mitotic activity index of 4T1 tumors by 37.5% (SAL 0.1) and 31.5% (SAL 1) vs. controls (set as a blank group with not applied salvia in the diet). In addition, salvia at higher doses significantly decreased necrosis/whole tumor area ratio by 46% when compared to control tumor samples. In a rat chemoprevention study, S. officinalis at a higher dose significantly lengthened the latency of tumors by 8.5 days and significantly improved the high/low-grade carcinomas ratio vs. controls in both doses. Analyses of the mechanisms of anticancer activities of S. officinalis included well-validated prognostic, predictive, and diagnostic biomarkers that are applied in both oncology practice and preclinical investigation. Our assessment in vivo revealed numerous significant changes after a comparison of treated vs. untreated cancer cells. In this regard, we found an overexpression in caspase-3, an increased Bax/Bcl-2 ratio, and a decrease in MDA, ALDH1, and EpCam expression. In addition, salvia reduced TGF-β serum levels in rats (decrease in IL-6 and TNF-α levels were with borderline significance). Evaluation of epigenetic modifications in rat cancer specimens in vivo revealed a decline in the lysine methylations of H3K4m3 and an increase in lysine acetylation in H4K16ac levels in treated groups. Salvia decreased the relative levels of oncogenic miR21 and tumor-suppressive miR145 (miR210, miR22, miR34a, and miR155 were not significantly altered). The methylation of ATM and PTEN promoters was decreased after S. officinalis treatment (PITX2, RASSF1, and TIMP3 promoters were not altered). Analyzing plasma metabolomics profile in tumor-bearing rats, we found reduced levels of ketoacids derived from BCAAs after salvia treatment. In vitro analyses revealed significant anti-cancer effects of SPGE extract in MCF-7 and MDA-MB-231 cell lines (cytotoxicity, caspase-3/-7, Bcl-2, Annexin V/PI, cell cycle, BrdU, and mitochondrial membrane potential). Our study demonstrates the significant chemopreventive and treatment effects of salvia haulm using animal or in vitro BC models.

• Publikační typ
• časopisecké články MeSH

Neuroendokrinní tumory představují heterogenní skupinu neoplazií vycházejících z různých anatomických lokalizací, přičemž přibližně 50 % je gastrointestinálního původu. Mezi klíčové parametry při hodnocení každého případu patří morfologie nádoru, počet mitotických buněk a index Ki-67. Smíšené adenoneuroendokrinní karcinomy (MANEC) jsou vzácné agresivní novotvary sestávající z adenokarcinomatózních i neuroendokrinních buněk, přičemž každá složka musí tvořit alespoň 30 % léze. Naším případem je 77letý polymorbidní pacient, který pro známky akutního krvácení do horní oblasti gastrointestinálního traktu s vyjádřeným anemickými syndromem podstoupil gastroskopické vyšetření s nálezem vředové léze na přední stěně žaludku na přechodu těla a antra. Při kontrolních gastroskopických vyšetřeních s odběrem biopsií byly nejdříve histologicky prokázány pouze známky chronické gastritidy při pozitivitě na Helicobacter pylori, následně nalezeny fragmenty high-grade tubulárního až tubulovilózního adenomu a struktury středně diferencovaného tubulárního adenokarcinomu. Histologickým rozborem žaludečního resekátu byl prokázán smíšený adenoneuroendokrinní karcinom s lymfangioinvazí.

Neuroendocrine tumours represent a heterogeneous group of neoplasia arising from different anatomical locations, with approximately 50% of gastrointestinal origin. Main parameters in the evaluation of each case include tumour morphology, mitotic cell count, and Ki-67 index. Mixed adeno-neuroendocrine carcinomas (MANECs) are rare aggressive neoplasms consisting of both adenocarcinomatous and neuroendocrine cells, each component constituting at least 30% of the lesion. Our case represents 77-year-old polymorbid patient who, due to signs of acute bleeding in the upper gastrointestinal tract with anaemic syndrome, underwent a gastroscopic examination for melena with the finding of an ulcer lesion on the front wall of the stomach at the junction of the body and the antrum. The control gastroscopic examinations with biopsies, at first only signs of chronic gastritis with Helicobacter pylori positivity were histologically proven, then fragments of high-grade tubular to tubulovillous adenoma and structures of moderately differentiated tubular adenocarcinoma were found. Histological analysis of the gastric resection showed mixed adeno-neuroendocrine carcinoma with lymphangioinvasion.

• MeSH
• adenokarcinom diagnóza   patologie   terapie   MeSH
• adjuvantní chemoterapie MeSH
• biopsie metody   MeSH
• diagnostické zobrazování metody   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• nádory žaludku * diagnóza   patologie   terapie   MeSH
• neuroendokrinní karcinom diagnóza   patologie   terapie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Osvojování jazyka a komunikace dítětem s Downovým syndromem bylo na poli české lingvistiky tématem dosud opomíjeným. Autorka s využitím nejnovějších poznatků o osvojování jazyka dětmi s typickým i netypickým vývojem popisuje specifika v budování jazykové a komunikační kompetence dětí s touto diagnózou. Ojedinělou součástí publikace je výzkum raného komunikačního chování chlapce vyrůstajícího v česko-německém jazykovém prostředí, na jehož základě autorka probírá osvědčené metody k rozvoji komunikace a porozumění. Monografie má také silný přesah etický.; Autorka s využitím nejnovějších poznatků o osvojování jazyka dětmi s Downovým syndromem popisuje specifika v budování jazykové a komunikační kompetence dětí s touto diagnózou.

• Klíčová slova
• Lingvistika,
• MeSH
• dětská psychologie MeSH
• Downův syndrom MeSH
• jazyk (prostředek komunikace) MeSH
• komunikace MeSH
• postižené děti MeSH
• vývoj dítěte MeSH

• NLK Obory
• psychologie, klinická psychologie
• lingvistika, lékařská terminologie

Salivary gland secretory carcinoma (SC), previously mammary analog SC, is a low-grade malignancy characterized by well-defined morphology and an immunohistochemical and genetic profile identical to SC of the breast. Translocation t(12;15)(p13;q25) resulting in the ETV6 :: NTRK3 gene fusion is a characteristic feature of SC along with S100 protein and mammaglobin immunopositivity. The spectrum of genetic alterations for SC continues to evolve. The aim of this retrospective study was to collect data of salivary gland SCs and to correlate their histologic, immunohistochemical, and molecular genetic data with clinical behavior and long-term follow-up. In this large retrospective study, we aimed to establish a histologic grading scheme and scoring system. A total of 215 cases of salivary gland SCs diagnosed between 1994 and 2021 were obtained from the tumor registries of the authors. Eighty cases were originally diagnosed as something other than SC, most frequently acinic cell carcinoma. Lymph node metastases were identified in 17.1% (20/117 cases with available data), with distant metastasis in 5.1% (6/117). Disease recurrence was seen in 15% (n=17/113 cases with available data). The molecular genetic profile showed ETV6 :: NTRK3 gene fusion in 95.4%, including 1 case with a dual fusion of ETV6 :: NTRK3 and MYB :: SMR3B . Less frequent fusion transcripts included ETV6 :: RET (n=12) and VIM :: RET (n=1). A 3-tiered grading scheme using 6 pathologic parameters (prevailing architecture, pleomorphism, tumor necrosis, perineural invasion (PNI), lymphovascular invasion (LVI), and mitotic count and/or Ki-67 labeling index) was applied. Grade 1 histology was observed in 44.7% (n=96), grade 2 in 41.9% (n=90), and grade 3 in 13.5% (n=29) of cases. Compared with low-grade and intermediate-grade SC, high-grade tumors were associated with a solid architecture, more prominent hyalinization, infiltrative tumor borders, nuclear pleomorphism, presence of PNI and/or LVI, and Ki-67 proliferative index >30%. High-grade transformation, a subset of grade 2 or 3 tumors, seen in 8.8% (n=19), was defined as an abrupt transformation of conventional SC into high-grade morphology, sheet-like growth, and a tumor lacking distinctive features of SC. Both overall survival and disease-free survival (5 and 10 y) were negatively affected by tumor grade, stage, and TNM status (each P <0.0001). SC is a low-grade malignancy with predominantly solid-microcystic growth patterns, driven by a gene fusion, most commonly ETV6 :: NTRK3 . There is a low risk for local recurrence and a good overall long-term survival, with a low risk for distant metastasis but a higher risk for locoregional lymph node metastasis. The presence of tumor necrosis, hyalinization, PNI and/or LVI, and positive resection margins correlate with higher tumor grade, less favorable prognosis, and increased mortality. The statistical results allowed us to design a 3-tiered grading system for salivary SC.

• MeSH
• antigen Ki-67 MeSH
• fúzní onkogenní proteiny genetika   metabolismus   MeSH
• lidé MeSH
• lokální recidiva nádoru genetika   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory slinných žláz * patologie   MeSH
• nekróza MeSH
• retrospektivní studie MeSH
• sekreční karcinom mamárního typu * genetika   MeSH
• slinné žlázy metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Agonisté receptoru pro GLP-1 (GLP-1 RA) v injekční formě patří podle doporučení ADA/EASD mezi první injekční terapii před bazálním inzulinem u pacientů s diabetes mellitus 2. typu, kteří nedosahují cílových hodnot kompenzace při terapii diabetickou dietou a perorálními antidiabetiky. Dulaglutid je dlouhodobě působící GLP-1 RA s aplikací 1x týdně, který úspěšně snižuje hodnotu glykovaného hemoglobinu HbA1c a hmotnost. Oproti inzulinu je terapie dulaglutidem spojena s nižším rizikem hypoglykemií, hmotnostních přírůstků a nevyžaduje složitou edukaci. Dávku není třeba titrovat a léčba je od počátku dobře snášena. Ve studii REWIND redukoval dulaglutid výskyt závažných KV příhod (MACE). Kazuistiky dokumentují dlouhodobou účinnost terapie dulaglutidem u diabetiků 2. typu v klinické praxi.

GLP-1 receptor agonists (GLP-1 RA) in injection form according to ADA/EASD recommendation rank among the first injection therapies preceding basal insulin in patients afflicted with type 2 diabetes who do not achieve target values of compensation during dietary therapy and peroral antidiabetics therapy. When applied once a week, dulaglutide is a long-term acting GLP-1 RA successfully reducing the glycated haemoglobin value HbA1c and weight. Compared to insulin, dulaglutide therapy is linked to a decreased risk of hypoglycaemia, lower weight accruals and does not impose demanding education. Dosage does not require titration while the therapy is right from the start well tolerated. Dulaglutide according to the REWIND study reduced the occurrence of serious CV events (MACE). In clinical practice case studies document the longterm efficacy of dulaglutide therapy for type 2 diabetes patients.

• Klíčová slova
• dulaglutid,
• MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   MeSH
• Downův syndrom komplikace   MeSH
• glukagonu podobné peptidy analogy a deriváty   MeSH
• glykovaný hemoglobin analýza   účinky léků   MeSH
• hypoglykemika * aplikace a dávkování   škodlivé účinky   MeSH
• index tělesné hmotnosti MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• mentální retardace komplikace   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Studying the anticancer activity of 5-arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones towards cell lines of different cancer types allowed the identification of hit-compounds inhibiting the growth of daunorubicin- (CEM-DNR, IC50 = 0.32-1.28 μM) and paclitaxel-resistant (K562-TAX, IC50 = 0.21-1.23 μM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF-CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site.

• MeSH
• apoptóza MeSH
• modulátory tubulinu * farmakologie   chemie   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• screeningové testy protinádorových léčiv MeSH
• tubulin metabolismus   MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH

Publikace se zaměřuje na verbální a neverbální komunikaci, vývoj řeči, a raný vývoj dětí s Downovým syndromem. Určeno odborné veřejnosti.; Autorka s využitím nejnovějších poznatků o osvojování jazyka dětmi s Downovým syndromem popisuje specifika v budování jazykové a komunikační kompetence dětí s touto diagnózou.

• MeSH
• dětská psychologie MeSH
• Downův syndrom MeSH
• jazyk (prostředek komunikace) MeSH
• komunikace MeSH
• postižené děti MeSH
• vývoj dítěte MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Vývojová psychologie. Individuální psychologie
• NLK Obory
• psychologie, klinická psychologie
• lingvistika, lékařská terminologie

Poorly differentiated chordoma is a newly recognized entity in the recent World Health Organization (WHO) classification of tumors of soft tissue and bone. Slightly over 60 such cases have been documented. Herein, we present a clinicopathological profile, including radiological features, of nine cases, which occurred in five males and four females, with age varying from 1 to 29 years (median = 43), in the cervical spine (n = 2), skull base (n = 2), clivus (n = 2), thoracic spine (n = 1) lumbar spine (n = 1) and coccyx (n = 1) Average tumor size was 4.8 cm. None of the 6-referral cases was diagnosed as a poorly differentiated chordoma at the referring laboratory. Histopathologically, all cases displayed a cellular tumor comprising polygonal cells (n = 9) displaying moderate to marked nuclear pleomorphism with prominent nucleoli (n = 7), eosinophilic (n = 9) to vacuolated cytoplasm (n = 7), rhabdoid morphology (n = 4), interspersed mitotic figures (n = 5), focal necrosis (n = 6) and inflammatory cells (n = 9). A single tumor displayed areas resembling classic chordoma, transitioning into poorly differentiated areas. There were multinucleate giant cells and physaliphorous cells in two tumors, each, respectively. Immunohistochemically, tumor cells were positive for AE1/AE3 (7/7), EMA (7/7), cytokeratin (CK) MNF116 (1/1), OSCAR (1/1), brachyury (9/9, diffusely), S100P (4/7, mostly focally), and glypican 3(2/4). SMARCB1/INI1 was completely lost in all nine tumors. A single case tested by FISH showed homozygous deletion of the SMARCB1 gene. Therapeutically (n = 7), all patients were treated with surgical resection (invariably incomplete) (n = 5), followed by adjuvant radiation therapy (n = 4) and chemotherapy (n = 4). While a single patient partially responded to treatment and another patient is alive with no evidence of disease after 23 years, three patients died of disease, six, eight, and 11 months post-diagnosis, despite adjuvant treatments. A single patient presented with a metastatic lung nodule, while another developed widespread metastasis. Poorly differentiated chordomas display a spectrum of features, are associated with a lower index of suspicion for a diagnosis, and display aggressive outcomes. Critical analysis of radiological and histopathological features, including necessary immunostains (brachyury and SMARCB1/INI1), is necessary for their timely diagnosis. These tumors show loss of SMARCB1/INI1 immunostaining and homozygous deletion of INI1/SMARCB1 gene.

• MeSH
• chordom * diagnóza   diagnostické zobrazování   genetika   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• gen SMARCB1 * analýza   genetika   MeSH
• imunohistochemie MeSH
• kojenec MeSH
• lidé MeSH
• metastázy nádorů patologie   MeSH
• mladiství MeSH
• nádorové biomarkery analýza   genetika   MeSH
• předškolní dítě MeSH
• sekvenční delece MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH