• MeSH
• Adult MeSH
• Gram-Positive Rods pathogenicity   MeSH
• Hemolysis MeSH
• Respiratory Tract Infections diagnosis   microbiology   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Lysine MeSH
• Microbial Sensitivity Tests methods   MeSH
• Adolescent MeSH
• Staphylococcus aureus MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Publication type
• Review MeSH
• Comparative Study MeSH

(1) Background: N-cadherin expression, epithelial-to-mesenchymal transition (EMT) and aggressive biological phenotype of tumor cells are linked although the underlying mechanisms are not entirely clear. (2) Methods: In this study, we used two different in vitro cell models with varying N-cadherin expression (stabilized lines and primocultures) and investigated their select biological features including the degree of their chemoresistance both in vitro as well as in vivo. (3) Results: We report that although enforced N-cadherin expression changes select morphological and behavioral characteristics of exposed cells, it fails to successfully reprogram cells to the aggressive, chemoresistant phenotype both in vitro as well as in vivo as verified by implantation of those cells into athymic mice. Conversely, primocultures of patient-colonic cells with naturally high levels of N-cadherin expression show fully aggressive and chemoresistant phenotype pertinent to EMT (in vitro and in vivo), with a potential to develop new mutations and in the presence of dysregulated regulatory pathways as represented by investigated miRNA profiles. (4) Conclusions: The presented results bring new facts concerning the functional axis of N-cadherin expression and related biological features of colon cancer cells and highlight colon cancer primocultures as a useful model for such studies.

• Publication type
• Journal Article MeSH

• MeSH
• Bacterial Adhesion MeSH
• Bacteriophages physiology   MeSH
• Epithelium microbiology   MeSH
• Cells, Cultured MeSH
• Ruminants MeSH
• Cattle MeSH
• Streptococcus physiology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH

• MeSH
• Rumen cytology   microbiology   MeSH
• Bacterial Adhesion MeSH
• Epithelium microbiology   MeSH
• Epithelial Cells MeSH
• Hydrogen-Ion Concentration MeSH
• Cattle MeSH
• Streptococcus bovis classification   metabolism   ultrastructure   MeSH
• Bacterial Typing Techniques MeSH
• Hydrocarbons pharmacology   MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

• MeSH
• Adult MeSH
• Glioblastoma metabolism   pathology   genetics   MeSH
• Glioma * metabolism   pathology   genetics   MeSH
• Hypoxia metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mice MeSH
• Biomarkers, Tumor metabolism   MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms metabolism   pathology   genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Aged MeSH
• STAT3 Transcription Factor * metabolism   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Mice MeSH
• Aged MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Currently, there is no clinical marker which allows a pre-therapeutic selection of patients with head and neck tumors that would profit more from the conservative therapy or primary surgery, respectively. We meaningfully contribute to solution of this "First Therapy Dilemma" by developing a method for in vitro detection of DNA breaks mediating the effects of (chemo)radiotherapy. By this method, we will sensitively determine the radiosensitivity of tumors before beginning the treatment, identify patients hypersensitive or resistant to radiation, and help to optimize the therapy. The method also enables us to elucidate the effectiveness of alternative irradiation regimes, explore and develop new therapeutic approaches (the replication stress induction and proton irradiation) and categorize patients for the best therapy. For the first time in this context, we compare primocultures of different cell types isolated from the tumor. Though, the main aim of this project remains to develop a cost-efficient, fast, robust, and easy to perform diagnostic method with a large room for automation.

V současnosti není znám klinický marker, který by umožňoval odlišit pacienty s nádory hlavy a krku, kteří budou více profitovat z konvenční léčby, od těch, kterým lépe poslouží chirurgický zákrok. V rámci projektu významně přispějeme k řešení tohoto "Dilematu první léčby" zavedením metody in vitro detekce zlomů DNA, jež zodpovídají za účinek konvenční (chemo)radioterapie. V našem výzkumu a v praxi tato metoda umožní velmi citlivě stanovit radiosensitivitu jednotlivých nádorů již před započetím léčby, spolehlivě odhalit pacienty hypersensitivní či rezistentní k záření a optimalizovat terapii. Takto vytipujeme nádory neodpovídající na současnou léčbu, u kterých budeme, opět s využitím zavedené metody, zkoumat účinnost alternativních režimů ozařování a nových terapií – indukce replikačního stresu a ozařování protony. Vůbec poprvé budeme uvedené problémy studovat na paralelních primokulturách různých buněčných typů vyizolovaných z nádoru. Hlavním cílem projektu však zůstává vývoj levné, rychlé, robustní a snadno proveditelné diagnostické metody s možnostmi automatizace.

• MeSH
• Molecular Diagnostic Techniques methods   MeSH
• Genetic Testing methods   MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Head and Neck Neoplasms diagnosis   genetics   therapy   MeSH
• DNA Damage genetics   MeSH
• Proton Therapy MeSH
• Radiotherapy methods   MeSH
• In Vitro Techniques MeSH
• Radiation Tolerance MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• onkologie
• genetika, lékařská genetika
• radiologie, nukleární medicína a zobrazovací metody
• NML Publication type
• závěrečné zprávy o řešení grantu AZV MZ ČR

Všeobecný pokrok v zaváděni účinných metod kontroly a léčby tuberkulózy v poválečném obdobi, především nástup etiotropních antituberkulotík, byl podnětem k nebývalému rozvoji mykobakteriologie v České republice. Vůdčí osobností se stal L. Sula, který vytvořil první českou „školu" mykobakteriologie a zasloužil se o její uplatnení na mezinárodním poli. Sám zavedl hromadné očkováni BCG a M vakcinou, navrhl testovaní postvakcinační alergie BCG a M testem, zavedl tekutou půdu k primokultivaci i stanovení lékové citlivosti, vytvořil sít diagnostických laboratoří se standardními metodikami aj. Národní referenční laboratoř pro mykobakteriologii byla zřízena v roce 1962, centrum pro tuberkulózní bakteriologii Světové zdravotnické organizace v roce 1964 a referenční laboratoř pro M. kansasii v roce 1986. V roce 1996 bylo v České repubhce celkem 36 laboratoří včetně osmi krajských, ve kterých pracovalo 171 pracovníků, včetně 37 s vysokoškolskou erudicí a v kterých bylo vyšetřeno více než 267 000 patologických vzorků. V metodologii průkazu mykobaktérií byly po roce 1990 zavedeny rychlé kultimolekulárně genetické techniky, v duhové identifikaci byly uplatněny metody in vitro, doplněné posléze o molekulárně genetické techniky, které se také uplatnily v epidemiologických studiích. V celorepublikovém měřítku byly zavedeny externí kontroly kvality. Od roku 1975 je využíván automatizovaný informační systém jako podklad pro monitorování laboratorních výsledků a k vykazování počtu bacilámích případů tuberkulózy a mykobakteriózy pro povinná hlášení v republikovém registru tuberkulózy.

The overall advances in the introduction of effective control methods and in the treatment of tuberculosis in the post-war period and, above all, the availability of aetiotropic antituberculosis drugs substantially stimulated the development of mycobacteriology in the Czech Republic. The leading personality in this field was L. Šula, who founded the first Czech ,,school" of mycobacteriology and was responsible for its international application. He initiated large-scale vaccination with the BCG and M vaccine, he proposed a post-vaccination BCG and M allergy test, he introduced into practice liquid media for primoculture and for the determination of drug sensitivity, he set up a whole network of diagnostic laboratories using standard methods etc. The National Reference Laboratory for Mycobacteriology was set up in 1962, the Centre of TB bacteriology of the WHO in 1964 and a reference laboratory for M. kansasii in 1986. In 1996 the Czech Republic had 36 laboratories, eight of them regional ones, With a staff of 171 (37 university graduates); they investigated more than 267 000 pathological samples. After 1990 the methods for the demonstration of mycobacteria could use rapid culture techniques and techniques of molecular genetics; in vitro identification methods were also introduced, later enhanced with the techniques of molecular genetics, which found their place also in epidemiological studies. Since 1975 the Czech Republic has an automated information system, basis for the monitoring of laboratory results and registration of bacillary TBC cases and of mycobacteriosis, required for the mandatory reporting of such cases in the National TBC Register.

• MeSH
• Drug Resistance, Microbial MeSH
• Antitubercular Agents MeSH
• Bacteriology history   MeSH
• BCG Vaccine MeSH
• Microbiological Techniques methods   MeSH
• Mycobacteriaceae pathogenicity   MeSH
• Tuberculosis diagnosis   drug therapy   prevention & control   MeSH
• Publication type
• Review MeSH

Studie srovnávala orální kolonizaci kvasinkovitými mikromycetami u 30 zdravých krevních dárců a 30 pacientů z jednotek intenzivní péče. U krevních dárců byla kolonizace zjištěna ve 47 %, většinou jen nízký počet kolonií. Masivní růst byl nalezen jen v 7 %. U 37 % dárců šlo jen o jeden druh kvasinky, u 10 % o smíšenou kolonizaci dvěma druhy. U pacientů z jednotek intenzivní péče byla kolonizace zjištěna v 74 %, ve 37 % masivní růst, ve 30 % smíšená kolonizace dvěma až čtyřmi druhy kvasinkovitých mikromycet. Při nálezu Candida albicans byla u 10 určených kolonií z primokultury (při menším počtu vyrostlých kolonií všechny kolonie) testována produkce sekrečních proteináz orientační metodou podle Staiba. U zdravých dárců i u pacientů z jednotek intenzivní péče se vyskytovaly proteináza-pozitivní i proteináza-negativní luneny C. albicans přibližně ve stejném poměru 1:1. Krevní dárci byli však kolonizovaní jen jedním biotypem, v jednom případě byly nalezeny oba typy současně. U pacientů z jednotek intenzivní péče byla u poloviny testovaných případů zjištěna smíšená kolonizace oběma biotypy. Studie upozorňuje na to, že u rizikových pacientů se objevuje větší pestrost v kvasinkové mykoflóře a koexistence biotypu C. albicans s různým stupněm potenciální virulence.

The authoi lors compared oral colonisation with yeast-like micromycetes in 30 healthy blood donors and 30 patients from intensive care units. In blood donors colonisation was found in 47 %, in the majority only a small number of colonies. Massive growth was found only in 7 %. In 37 % of donors only one type of yeast was involved, in 10 % a mixed colonisation with two types. In patients from intensive care units colonisation was found in 74 %, in 37 % massive growth, in 30 % mixed colonisation with two to four types of yeast-like micromycetes. When Candida albicans was found, in 10 colonies from the primoculture (in case of a smaller number of colonies in all colonies) production of secretory proteinases were tested by the orientational method as described by Staib. In healthy donors and in patients trom tne intensive care unit protein-positive and protein-negative strains of c. albicans were found in approximately the same ratio 1:1. Blood donors were however colonized only by one biotype, in one case both types were present. In patients from intensive care units in half the tested cases a mixed colonisation with both biotypes was found. The investigation draws attention to the fact that in risk patients there is a greater variety in the yeast microflora and coexistence of biotypes of C. albicans with different grades of potential virulence.

• MeSH
• Candida albicans pathogenicity   MeSH
• Blood Donors MeSH
• Intensive Care Units MeSH
• Yeasts pathogenicity   MeSH
• Humans MeSH
• Oral Health MeSH
• Inpatients MeSH
• Virulence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comparative Study MeSH