• MeSH
• Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics   MeSH
• Cell Cycle drug effects   MeSH
• Gene Expression drug effects   MeSH
• Research Support as Topic MeSH
• Genes, p53 drug effects   MeSH
• Immunochemistry MeSH
• Humans MeSH
• Methotrexate pharmacology   MeSH
• Tumor Suppressor Protein p53 drug effects   MeSH
• Roscovitine MeSH
• Oligonucleotide Array Sequence Analysis methods   MeSH
• In Vitro Techniques MeSH
• Check Tag
• Humans MeSH

The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential.

• MeSH
• Cell Cycle drug effects   physiology   MeSH
• Genes, Neoplasm physiology   MeSH
• Glycine N-Methyltransferase metabolism   MeSH
• Humans MeSH
• Mice, Inbred BALB C MeSH
• Mice, Nude MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms metabolism   physiopathology   MeSH
• Polymerase Chain Reaction MeSH
• Gene Expression Regulation, Neoplastic drug effects   physiology   MeSH
• Sarcosine metabolism   pharmacology   MeSH
• Sarcosine Dehydrogenase metabolism   MeSH
• Transcriptome MeSH
• Neoplasm Transplantation MeSH
• Up-Regulation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Blastocrithidia papi sp. n. is a cyst-forming trypanosomatid parasitizing firebugs (Pyrrhocoris apterus). It is a member of the Blastocrithidia clade and a very close relative of B. largi, to which it is almost identical through its SSU rRNA gene sequence. However, considering the SL RNA gene these two species represent quite distinct, not even related typing units. Morphological analysis of the new species revealed peculiar or even unique features, which may be useful for future taxonomic revision of the genus Blastocrithidia. These include a breach in the microtubular corset of rostrum at the site of contact with the flagellum, absence of desmosomes between flagellum and rostrum, large transparent vacuole near the flagellar pocket, and multiple vacuoles with fibrous content in the posterior portion of the cell. The study of the flagellates' behavior in the host intestine revealed that they may attach both to microvilli of enterocytes using swollen flagellar tip and to extracellular membranes layers using hemidesmosomes of flagellum. Laboratory experiments on B. papi transmission in P. apterus demonstrated that the parasite may be transmitted vertically (via contaminated surface of eggs) and horizontally (via contaminated substrate and/or necrophagy). We argue that the parasite exploits transmission mechanisms intended for obligate bacterial symbionts of P. apterus.

• MeSH
• Heteroptera microbiology   parasitology   MeSH
• Life Cycle Stages * MeSH
• Intestines parasitology   MeSH
• Trypanosomatina classification   cytology   physiology   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH

Článek informuje o možnostech současné medicíny a životního stylu jedince, jak ovlivnit délku i kvalitu života.

The paper informs about possibilities of present medicine, but also individual life style, to influence the length and quality of our life.

• MeSH
• Cell Cycle physiology   genetics   MeSH
• Epidemiologic Studies MeSH
• Financing, Organized MeSH
• Genetic Phenomena physiology   genetics   immunology   MeSH
• Caloric Restriction MeSH
• Humans MeSH
• Evidence-Based Medicine trends   MeSH
• Metformin metabolism   MeSH
• Interdisciplinary Communication MeSH
• Obesity genetics   metabolism   pathology   MeSH
• Protein Kinases physiology   genetics   MeSH
• Sirtuins physiology   genetics   MeSH
• Aging physiology   genetics   MeSH
• Stilbenes metabolism   MeSH
• Age Factors MeSH
• Life Style MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

UNLABELLED: Comparing the gene expression profiles of metastatic and nonmetastatic cells has the power to reveal candidate metastasis-associated genes, whose involvement in metastasis can be experimentally tested. In this study, differentially expressed genes were explored in the v-src-transformed metastatic cell line PR9692 and its nonmetastatic subclone PR9692-E9. First, the contribution of homeodomain only protein X (HOPX) in metastasis formation and development was assessed. HOPX-specific knockdown decreased HOPX expression in the nonmetastatic subclone and displayed reduced cell motility in vitro. Critically, HOPX knockdown decreased the in vivo metastatic capacity in a syngeneic animal model system. Genomic analyses identified a cadre of genes affected by HOPX knockdown that intersected significantly with genes previously found to be differentially expressed in metastatic versus nonmetastatic cells. Furthermore, 232 genes were found in both screens with at least a two-fold change in gene expression, and a number of high-confidence targets were validated for differential expression. Importantly, significant changes were demonstrated in the protein expression level of three metastatic-associated genes (NCAM, FOXG1, and ITGA4), and knockdown of one of the identified HOPX-regulated metastatic genes, ITGA4, showed marked inhibition of cell motility and metastasis formation. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns. IMPLICATIONS: This study provides new mechanistic insight into a HOPX-regulated metastatic dissemination signature.

• MeSH
• Cell Cycle MeSH
• Down-Regulation MeSH
• Sarcoma, Experimental genetics   pathology   secondary   MeSH
• Forkhead Transcription Factors genetics   metabolism   MeSH
• Gene Knockdown Techniques MeSH
• Genes, src MeSH
• Homeodomain Proteins genetics   metabolism   MeSH
• Chickens MeSH
• Neoplasm Metastasis genetics   MeSH
• Neural Cell Adhesion Molecules genetics   metabolism   MeSH
• Cell Transformation, Neoplastic genetics   MeSH
• Cell Line, Tumor MeSH
• Cell Movement MeSH
• Avian Proteins genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Oligonucleotide Array Sequence Analysis MeSH
• Gene Expression Profiling MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The most recent genome-editing system called CRISPR-Cas9 (clustered regularly interspaced short palindromic repeat system with associated protein 9-nuclease) was employed to delete four non-essential genes (i.e., Caeco1, Caidh1, Carom2, and Cataf10) individually to establish their gene functionality annotations in pathogen Candida albicans. The biological roles of these genes were investigated with respect to the cell wall integrity and biogenesis, calcium/calcineurin pathways, susceptibility of mutants towards temperature, drugs and salts. All the mutants showed increased vulnerability compared to the wild-type background strain towards the cell wall-perturbing agents, (antifungal) drugs and salts. All the mutants also exhibited repressed and defective hyphal growth and smaller colony size than control CA14. The cell cycle of all the mutants decreased enormously except for those with Carom2 deletion. The budding index and budding size also increased for all mutants with altered bud shape. The disposition of the mutants towards cell wall-perturbing enzymes disclosed lower survival and more rapid cell wall lysis events than in wild types. The pathogenicity and virulence of the mutants was checked by adhesion assay, and strains lacking rom2 and eco1 were found to possess the least adhesion capacity, which is synonymous to their decreased pathogenicity and virulence.

• MeSH
• Acetyltransferases deficiency   genetics   physiology   MeSH
• Antifungal Agents pharmacology   MeSH
• Cell Adhesion MeSH
• Cell Wall drug effects   MeSH
• Cell Cycle MeSH
• Candida albicans drug effects   genetics   pathogenicity   physiology   MeSH
• Chitinases pharmacology   MeSH
• CRISPR-Cas Systems MeSH
• Gene Deletion MeSH
• Glucan Endo-1,3-beta-D-Glucosidase pharmacology   MeSH
• TATA-Binding Protein Associated Factors deficiency   genetics   physiology   MeSH
• Fungal Proteins genetics   physiology   MeSH
• Genes, Fungal * MeSH
• Hyphae growth & development   MeSH
• Isocitrate Dehydrogenase deficiency   genetics   physiology   MeSH
• Cations pharmacology   MeSH
• Reproduction, Asexual MeSH
• Open Reading Frames MeSH
• DNA Damage MeSH
• Calcium physiology   MeSH
• Virulence genetics   MeSH
• Publication type
• Journal Article MeSH

Východiská: Mozgové nádory tvoria rôznorodú skupinu malignít charakterizovaných intertumorálnou aj intratumorálnou heterogenitou. Medzi najagresívnejší z nich radíme glioblastóm, ktorý je napriek pokrokom v súčasnej medicíne stále neliečiteľný. Jedným z dôvodov je vysoký stupeň rekurencie ochorenia a rezistencia na štandardne využívané chemoterapeutikum temozolomid. Preto mapovanie dráh zodpovedných za tumorigenézu na transkripčnej úrovni môže prispieť k determinovaniu príčin a stupňa agresivity medzi jednotlivými typmi gliálnych malignít. Súbor pacientov a metódy: Do súboru vzoriek boli zaradené biopsie od pacientov s astrocytómom (n = 6), glioblastómom (n = 22) a meningiómom (n = 14). Kontrolnú skupinu predstavovali RNA izolované zo zdravého ľudského mozgu (n = 3). Reverznou transkripciou získanú cDNA sme využili na kvantitatívnu analýzu pomocou Human Cancer PathwayFinder™ real-time PCR Array v 96 jamkovom formáte a pre každú vzorku sme stanovili expresiu 84 génov patriacich do 9 regulačných dráh (angiogenéza, apoptóza, bunkový cyklus a starnutie, poškodenie a oprava DNA, epiteliálno-mezenchymálny prechod, hypoxia, celkový metabolizmus a dynamika telomér). Výsledky: Určením relatívnej expresie vybraných génov sme charakterizovali profil jednotlivých mozgových malignít v kontexte signálnych dráh ovplyvňujúcich tumorigenézu. Zo všetkých sledovaných génov jednotlivých dráh sme zaznamenali dereguláciu u glioblastómov v 50 %, u meningiómov v 52,4 % a u astrocytómov v 53,6 %. Celkovo sme najvýraznejšie zmeny so štatistickou signifikanciou oproti kontrole zaznamenali u génov spájaných s epiteliálno-mezenchymálnou tranzíciou (CDH2, FOXC2, GSC, SNAI2 a SOX10), bunkovým starnutím (BMI1, ETS2, MAP2K1 a SOD1), opravou DNA (DDB2, ERCC3, GADD45G a LIG4) a dynamikou telomér (TEP1, TERF2IP, TNKS a TNKS2). Záver: Na základe získaných dát môžeme konštatovať, že jednotlivé diagnózy sa líšia v transkriptomickom profile. Prihliadnúc na tento fakt, je preto nevyhnutná potreba individuálneho molekulového prístupu s cieľom komplexnej a cielenej terapie na viacerých stupňoch nádorového metabolizmu.

Background: Brain tumors are a heterogeneous group of malignancies characterized by inter- and intratumoral heterogeneity. Among them, the most aggressive and, despite advances in medicine, still incurable remains glioblastoma. One of the reasons is the high recurrence rate of the disease and resistance to temozolomide, a golden standard in chemotherapy of brain tumors. Therefore, mapping the pathways responsible for tumorigenesis at the transcriptional level may help to determine the causes and aggressive behavior among different glial tumors. Patients and methods: Biopsies from patients with astrocytoma (N = 6), glioblastoma (N = 22), and meningioma (N = 14) were included in the sample set. A control group consisted of RNA isolated from healthy human brain (N = 3). The reverse-transcribed cDNAs were analyzed using the Human Cancer PathwayFinder™ real-time PCR Array in a 96-well format. The expression of 84 genes belonging to 9 signaling pathways (angiogenesis, apoptosis, cell cycle and senescence, DNA damage and repair, epithelial-to-mesenchymal transition, hypoxia, overall metabolism, and telomere dynamics) was determined for each sample. Results: By determining the relative expression of selected genes, we characterized the transcriptomic profile of individual brain malignancies in the context of signaling pathways involved in tumorigenesis. We observed deregulation in 50, 52.4 and 53.6% % of the genes in glioblastomas, meningiomas and astrocytomas, respectively. The most pronounced changes with statistical significance compared to control were observed in the genes associated with epithelial-to-mesenchymal transition (CDH2, FOXC2, GSC, SNAI2, and SOX10), cellular senescence (BMI1, ETS2, MAP2K1, and SOD1), DNA repair (DDB2, ERCC3, GADD45G, and LIG4), and dynamic of telomeres (TEP1, TERF2IP, TNKS, and TNKS2). Conclusion: Based on the obtained data, we can conclude that individual diagnoses differ in transcriptomic profile. An individual molecular approach is therefore necessary in order to provide comprehensive and targeted therapy on multiple metabolic pathways in the diagnosis of brain tumors.

• MeSH
• Clinical Studies as Topic MeSH
• Humans MeSH
• MicroRNAs analysis   MeSH
• Brain Neoplasms * genetics   MeSH
• Check Tag
• Humans MeSH

Superfamily of cytochrome P450 enzymes (CYPs), a distinctive enzyme system by which human body defends itself against toxic compounds, is the subject of a complex regulation process involving various mechanisms, on the levels of expression and activity. Apart from physiological factors, several patho-physiological ones such as inflammation, infection, and stress affect CYP expression. The aim of this review is to summarize the current knowledge on the role of microtubules network in the regulation of drug metabolizing CYPs. Experiments on human and animal cell models revealed that microtubules disruption severely impaired basal and inducible expression of human CYP 1A1, 2B6, 2C8, 2C9, 2C19, and 3A4, and rat CYP 1A2, 2B1, 2B2, and 3A23. Inhibition of aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) transcriptional activity by microtubules disarray was found to be responsible for the suppressed CYP enzymes expression. However, the mechanism by which microtubules interfering agents (MIAs) inhibit GR and AhR transcriptional activities is not fully understood yet. Several lines of evidence indicate that: i) the cell cycle, G2/M phase in particular, has an influence on AhR and GR transcriptional activity, and ii) MIAs negatively modulate GR transcriptional activity via the activation of c-Jun-N-terminal kinase. In conclusion, down-regulation of major CYP enzymes by microtubules disarray is intriguing from the mechanistic point of view and in relation to the cell differentiation.

• MeSH
• Models, Biological MeSH
• Humans MeSH
• Microtubules physiology   MeSH
• Gene Expression Regulation, Enzymologic MeSH
• Cytochrome P-450 Enzyme System genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH

Stastny, P, Lehnert, M, De Ste Croix, M, Petr, M, Svoboda, Z, Maixnerova, E, Varekova, R, Botek, M, Petrek, M, Lenka, K, and Cięszczyk, P. Effect of COL5A1, GDF5, and PPARA genes on a movement screen and neuromuscular performance in adolescent team sport athletes. J Strength Cond Res 33(8): 2057-2065, 2019-The risk of injury increases with adolescents' chronological age and may be related to limited muscle function neuromuscular, genetic, and biomechanical factors. The purpose of this study was to determine whether COL5A1, PPARA, and GDF5 genes are associated with muscle functions and stretch-shortening cycle performance in adolescent athletes. One hundred forty-six youth players (14.4 ± 0.2 years) from various team sports (basketball n = 54, soccer n = 50, handball n = 32) underwent a manual test for muscle function, maturity estimation, functional bend test (FBT), passive straight leg raise (SLR) test, leg stiffness test, test of reactive strength index (RSI), and gene sampling for COL5A1, PPARA, and GDF5. The χ test did not show any differences in allele or genotype frequency between participants before and after peak height velocity. Multivariate analysis of variance showed that COL5A1 rs12722 CT heterozygotes had worse score in FBT (p < 0.001), worse score in SLR (p = 0.003), and lower maturity offset (p = 0.029, only in females) than TT homozygotes. Male GDF5 rs143383 GG homozygotes showed better score in SLR than AA and AG genotypes (p = 0.003), and AA and AG genotypes in both sex had greater RSI than GG homozygotes (p = 0.016). The PPARA rs4253778 CC homozygotes had greater RSI than GG and GC genotypes (p = 0.004). The CT genotype in COL5A1 rs12722 is possible predictor of functional movement disruption in the posterior hip muscle chain, causing shortening in FBT and SLR, which includes hamstrings function. CT genotype in COL5A1 rs12722 should be involved in programs targeting hamstring and posterior hip muscle chain.

• MeSH
• Biomechanical Phenomena MeSH
• Genotype MeSH
• Collagen Type V genetics   MeSH
• Muscle, Skeletal metabolism   MeSH
• Humans MeSH
• Adolescent MeSH
• Movement physiology   MeSH
• PPAR alpha genetics   MeSH
• Cross-Sectional Studies MeSH
• Puberty physiology   MeSH
• Growth Differentiation Factor 5 genetics   MeSH
• Sex Factors MeSH
• Youth Sports physiology   MeSH
• Athletes * MeSH
• Muscle Strength MeSH
• Body Weights and Measures MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Amplified MYCN, common in neuroblastomas, can be detected as double minutes (dmin) or homogenously staining chromosomal regions (hsr). Expulsion of amplified MYCN has only been described in dmin. We used hydroxyurea (HU), which accelerates the expulsion of amplified genes and cytostatics (used in neuroblastoma therapy), to describe MYCN amplification changes after chemotherapy. We used IMR-32, SK-N-AS, UKF-NB-2, UKF-NB-3, UKF-NB-4, and derived sublines resistant to doxorubicin, cisplatin, and vincristine. The loss of amplified MYCN copies was investigated using comparative genomic hybridization and by fluorescent in situ hybridization. We found expulsion of amplified MYCN from hsr in UKF-NB-4 and IMR-32 cell lines, and determined the exact number of amplified MYCN copies. After the first cultivation with HU, some amplified MYCN was lost. UKF-NB-4 lost 20 copies on average, and IMR-32 lost 15 copies (P<0.001). After the second cultivation, cells without MYCN amplification were found. In comparison to sensitive cell lines, drug-resistant cell lines lost 17 copies on average. Our data show that expulsion of amplified MYCN genes is also possible from hsr and may be induced, not only by HU, but by other cytostatics as well.

• MeSH
• Cell Cycle MeSH
• Cisplatin administration & dosage   MeSH
• Doxorubicin administration & dosage   MeSH
• Genes, myc MeSH
• In Situ Hybridization, Fluorescence MeSH
• Hydroxyurea administration & dosage   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Neuroblastoma genetics   pathology   MeSH
• Antineoplastic Combined Chemotherapy Protocols administration & dosage   MeSH
• Vincristine administration & dosage   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH