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Search results for: G2/M ARREST
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Induction of G2/M phase arrest and apoptosis of human leukemia cells by potent antitumor triazoloacridinone C-1305
PublicationWykazaliśmy, że pochodna triazoloakrydonu C-1305 w stężeniach biologicznie istotnych indukuje blok cyklu komórkowego w fazie G2/M i apoptozę w komórkach białaczek ludzkich MOLT4 i HL60. Zjawisko apoptozy zostało określone na podstawie charakterystycznych zmian morfologicznych jak i biochemicznych tj. fragmentacji DNA, aktywacji kaspazy 3, cięcia PARP, spadku potencjału mitochondrialnego i ATP oraz eksternalizacji fosfatydyloseryny.
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Induction of G2/M phase arrest and apoptosis of human pancreatic cancer BxPC-3 cells by potenet antitumor 1-nitroacridine derivative C-1748
PublicationPancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine treatment results in only a marginal survival advantage. Thus, there is a strong need for the continuous development of novel therapeutic agents...
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The influence of G2 arrest abrogation on the long-term cytotoxicity of different genotoxic lesions
PublicationJak się uważa, zdolność komórek nowotworowych z uszkodzeniami DNA do zatrzymywania progresji w cyklu komórkowym w fazie G2 wydłuża czas na reperację tych uszkodzeń i zwiększa zdolność do przeżycia tych komórek. W pracy badaliśmy wpływ skrócenia bloku w fazie G2 w komórkach dwóch typów białaczek, poddanych działaniu związków przeciwnowotworowych indukujących różne typy uszkodzeń DNA, na efekt cytotoksyczny tych związków. Zwiększenie...
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Influence of G2 arrest on the cytotoxicity of DNA topoisomerase inhibitorstoward human carcinoma cells with different p53 status
PublicationRola bloku G2 w efekcie cytotoksycznym inhibitorów DNA topoizomeraz w stosunku do ludzkich komórek rakowych różniących się funkcjonalnością białka p53.
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Modulation of G2 arrest enhances cell death induced by the antitumor 1-nit-roacridine derivative, Nitracrine
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Increased susceptibility of PARP-1 KO cells to antitumor triazoloacridone C-1305 is associated with permanent G2 cell cycle arrest.
PublicationTriazoloakrydon C-1305 jest nowym inhibitorem topoizomerazy II wykazującym wysoką aktywność przeciwnowotworową. W tej pracy badaliśmy działanie cytotoksyczne pochodnej C-1305 i jej analogu strukturalnego C-1533 wobec komórek fibroblastów mysich i dwóch mutantów, w których uszkodzono gen PARP-1. Jak wykazaliśmy, komórki z uszkodzonym genem PARP-1 są nadwrażliwe na działanie związku C-1305 w porównaniu z komórkami PARP-1 +/+ podczas...
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From DNA damage to G2 arrest: the many roles of topoisomerase II. W: Prog-ress in Cell Cycle Research. Ed. Meijer L., Jezequel A., Roberge M. London: Plenum Publ. Comp. Ltd**2003 vol. 5 chapt. 30 s. 295-300 Od uszkodzeń DNA do bloku w G2: wiele ról dla topoizomerazy II.
PublicationInhibitory DNA topoizomerazy II sa jednymi z najbardziej szeroko stosowanymi lekami przeciwnowotworowymi. Związki te indukuja pekniecia nici DNA i bloku progresji cyklu komorkowego w fazie G2. Jednak topoizomeraza II jest nie tylko celem molekularnym dla lekow przeciwnowtworowych ale enzym ten pelniwazna role w odpowiedzi komorkowej na dzialanie wielu lekow uszkadzajacych DNA. Topoizomeraza tworzy kompleksy molekularne z bialkami...
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Triazoloacridone C-1305 abrogates the restriction checkpoint in cells lacking functional p53 and promotes their accumulation in the G2/M phase of the cell cycle
PublicationTriazoloakrydon C-1305, nowy inhibitor topoizomerazy II, wykazuje wysoką aktywość cytotoksyczną wobec komórek wielu typów nowotworów. Komórki mysie pozbawione genu PARP-1 wykazywały nadwrażliwość na działanie tego związku. W pracy testowaliśmy działanie związku wobec dwóch różnych komóek nowotworowych różniących się statusem p53: komórkami białaczki myelocytarnej HL-60 i raka sutka MCF-7. Wykazaliśmy, że inkubacja ze związkiem...
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Down-regulation of DNA topoisomerase IIalpha leads to prolonged cell cycle transit in G2 and early M phases and increased survival to microtubule-interacting agents
PublicationInhibitory polimeryzacji mikrotubul wykazują preferencyjną toksyczność wobec komórek mitotycznych. W ramach tego projektu badaliśmy czy oporność komórek ludzkich białaczek na inhibitor mikrotubul, winkrystynę, prowadzi do zmian w regulacji progresji cyklu komórkowego. Nasze wyniki wskazują, że oporności na winkrystynę towarzyszą zmiany w długości fazy G2 i M w nieobecności i obecności inhibitora wrzeciona mitotycznego, nokodazolu....
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<p>Mechano-signalling, induced by fullerene C<sub>60</sub> nanofilms, arrests the cell cycle in the G2/M phase and decreases proliferation of liver cancer cells</p>
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Rola bloku w fazach G2 i/lub M cyklu komórkowego w indukcji apoptozy w ko-mórkach nowotworowych z nieczynnym P53**2002, 116 s. 28 rys. bibliogr. 227 poz. maszyn. Rozprawa doktorska....Promotor: prof. dr hab. J. Konopa
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Cardinal regenerative features of the MRL mouse
PublicationIn this review, we discuss recent studies relating to major features of adult MRL mouse biology that contribute to the regenerative responses seen. These include an increased inflammatory cell profile, a unique glycolytic metabolic state typically found during embryogenesis, and a cell cycle phenotype of DNA damage and G2/M arrest. These traits have been found in other mammalian and non-mammalian regenerative systems. How these...
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DNA-damaging imidazoacridinone C-1311 induces autophagy followed by irreversible growth arrest and senescence in human lung cancer cells
PublicationImidazoacridinone 5-diethylaminoethylamino-8-hydroxyimidazoacridinone (C-1311) is an antitumor inhibitor of topoisomerase II and FMS-like tyrosine kinase 3 receptor. In this study, we describe the unique sequence of cellular responses to C-1311 in human non-small cell lung cancer (NSCLC) cell lines, A549 and H460. In A549 cells, C-1311 (IC80 = 0.08 µM) induced G1 and G2/M arrests, whereas H460 cells (IC80 = 0.051 µM) accumulated...
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Synthesis, Molecular Structure, Anticancer Activity, and QSAR Study of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)Benzenesulfonamide Derivatives
PublicationA series of N-(aryl/heteroaryl)-4-(1H-pyrrol-1-yl)benzenesulfonamides were synthesized from 4-amino-N-(aryl/heteroaryl)benzenesulfonamides and 2,5-dimethoxytetrahydrofuran. All the synthesized compounds were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. Compound 28, bearing 8-quinolinyl moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines,...
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Tetrahydroquinolinone derivatives exert antiproliferative effect on lung cancer cells through apoptosis induction
PublicationThe anticancer properties of quinolones is a topic of interest among researchers in the scientific world. Because these compounds do not cause side effects, unlike the commonly used cytostatics, they are considered a promising source of new anticancer drugs. In this work, we designed a brief synthetic pathway and obtained a series of novel 8-phenyltetrahydroquinolinone derivatives functionalized with benzyl-type moieties at position...
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Increased cytotoxicity of an unusual DNA topoisomerase II inhibitor compound C-1305 toward HeLa cells with downregulated PARP-1 activity results from re-activation of the p53 pathway and modulation of mitotic checkpoints
PublicationOur previous studies have shown that murine fibroblast cells, in which PARP-1 gene was inactivated by gene disruption, are extremely sensitive to triazoloacridone compound C-1305, an inhibitor of DNA topoisomerase II with unusual properties. Here, we show that pharmacological inhibition of PARP-1 activity by its inhibitor compound NU1025, sensitizes human cervical carcinoma HeLa cells to compound C-1305 compared to treatment with...
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Improved cytotoxicity and preserved level of cell death induced in colon cancer cells by doxorubicin after its conjugation with iron-oxide magnetic nanoparticles
PublicationA promising strategy for overcoming the problem of limited efficacy in antitumor drug delivery and in drug release is the use of a nanoparticle-conjugated drug. Doxorubicin (Dox) anticancer chemotherapeutics has been widely studied in this respect, because of severe cardiotoxic side effects. Here, we investigated the cytotoxic effects, the uptake process, the changes in cell cycle progression and the cell death processes in the...
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CYP3A4 overexpression enhances apoptosis induced by anticancer agent imidazoacridinone C-1311, but does not change the metabolism of C-1311 in CHO cells
PublicationWe examine whether CYP3A4 overexpression influences the rate and pattern of antitumor imidazoacridinone C-1311 metabolism, in relation to the impact of this overexpression on cell cycle progression and final cellular response of CHO cells following C-1311 treatment. Methods: Three CHO cell lines: CHO-WT, wild type, CHO-HR, overexpressing cytochrome P450 reductase (CPR) and CHO-HR-3A4, coexpressing CPR and CYP3A4 were applied....
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Exploring the Antitumor Efficacy of N-Heterocyclic Nitrilotriacetate Oxidovanadium(IV) Salts on Prostate and Breast Cancer Cells
PublicationThe crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H2O)](H2O)2 (I) and [(acr)H][VO(nta)(H2O)](H2O)2 (II), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts— 1,10-phenanthrolinium, [(phen)H][VO(nta)(H2O)](H2O)0.5 (III), 2,2′-bipyridinium [(bpy)H][VO(nta)(H2O)](H2O) (IV), and two newly synthesized compounds...
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New 2-[(4-Amino-6-N-substituted-1,3,5-triazin-2-yl)methylthio]-N-(imidazolidin-2-ylidene)-4-chloro-5-methylbenzenesulfonamide Derivatives, Design, Synthesis and Anticancer Evaluation
PublicationIn the search for new compounds with antitumor activity, new potential anticancer agents were designed as molecular hybrids containing the structures of a triazine ring and a sulfonamide fragment. Applying the synthesis in solution, a base of new sulfonamide derivatives 20–162 was obtained by the reaction of the corresponding esters 11–19 with appropriate biguanide hydrochlorides. The structures of the compounds were confirmed...
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Modulation of CYP3A4 activity and induction of apoptosis, necrosis and senescence by the antitumor imidazoacridinone C-1311 in human hepatoma cells
PublicationThere is increasing evidence that the expression level of drug metabolic enzymes affects the final cellular response following drug treatment. Moreover, anti-tumour agents may modulate enzymatic activity and/or cellular expression of metabolic enzymes in tumour cells. We investigated the influence of CYP3A4 overexpression on the cellular response induced by the anti-tumour agent C-1311 in hepatoma cells. C-1311-mediated CYP3A4...
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Antitumor 1-nitroacridine derivative C-1748 induces significant apoptosis in pancreatic cancer cells.
PublicationPancreatic cancer is the fifth leading cause of cancer death and has the lowest survival rate of any solid cancer in the industrial countries. The poor prognosis of pancreatic cancer results from its tendency for late presentation, aggressive invasion, early metastasis, and resistance to chemotherapy. Gemcitabine still remains the best chemotherapeutic agent available for the treatment of advanced pancreatic cancer. However, gemcitabine...
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Targeting of FLT3-ITD kinase contributes to high selectivity of imidazoacridinone C-1311 against FLT3-activated leukemia cells
PublicationDrugs targeting receptor tyrosine kinase FLT3 are of particular interest since activating FLT3-internal tandem duplication (ITD) mutations abundantly occur in fatal acute myeloid leukemias (AMLs). Imidazoacridinone C-1311, a DNA-reactive inhibitor of topoisomerase II, has been previously shown to be a potent and selective inhibitor of recombinant FLT3. Here, we expand those findings by studying its effect on leukemia cells with...
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Antitumor imidazoacridinone derivative C-1311 induces cell cycle arrest and cellular senescence-like phenotypic changes in human non-small lung A549 cancer cells
PublicationPrzeprowadzone badania miały na celu zbadanie rodzaju odpowiedzi komórkowej indukowanej przez pochodną C1311 w komórkach ludzkiego, niedrobnokomórkowego raka płuc A549, wyselekcjonowanych do badań ze względu na wysoką wrażliwość na działanie pochodnej C-1311. Wszystkie eksperymenty przeprowadzone zostały przy stężeniu hamującym proliferację komórek nowotworowych w 80%. Badania z wykorzystaniem techniki cytometrii przepływowej oraz...
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Metabolic transformation of antitumor acridinone C-1305 but not C-1311 via selective cellular expression of UGT1A10 increases cytotoxic response: implications for clinical use.
PublicationThe acridinone derivates C-1305 and C-1311 are promising antitumor agents with high activity against several experimental cellular and tumor models and which are under evaluation in pre-clinical and early phase clinical trials. Recent evidence from our laboratories has indicated that both compounds were conjugated by several UGT isoforms with the most active being extrahepatic UGT1A10. The present studies were designed to test...
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Utilizing Genome-Wide mRNA Profiling to Identify the Cytotoxic Chemotherapeutic Mechanism of Triazoloacridone C-1305 as Direct Microtubule Stabilization
PublicationRational drug design and in vitro pharmacology profiling constitute the gold standard in drug development pipelines. Problems arise, however, because this process is often dicult due to limited information regarding the complete identification of a molecule’s biological activities. The increasing aordability of genome-wide next-generation technologies now provides an excellent opportunity to understand a compound’s diverse eects...
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Molecular basis for the DNA damage induction and anticancer activity of asymmetrically substituted anthrapyridazone PDZ-7
Publicationnthrapyridazones, imino analogues of anthraquinone, constitute a family of compounds with remarkable anti-cancer activity. To date, over 20 derivatives were studied, of which most displayed nanomolar cytotoxicity towards broad spectrum of cancer cells, including breast, prostate and leukemic ones. BS-154, the most potent derivative, had IC50 values close to 1 nM, however, it was toxic in animal studies. Here, we characterize another...
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Synthesis, structure and physical properties of Ru ferrites: BaMRu5O11 (M= Li and Cu) and BaM'2Ru4O11 (M'=Mn, Fe and Co)
PublicationW pracy opisano syntezę, strukturę i właściwości fizyczne pięciu nowych związków z rodziny ferrytów na bazie Ru, których wzór chemiczny jest BaMRu5O11 (M = Li, Cu) i BaM'2Ru4O11 (M' = Mn, Fe, Co).
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Reactions of tBu2P-PLi-P(tBu)2 with [(Et3P)2MCl2] (M = Ni, Pd, Pt). Synthesis and properties of [(1,2-h-tBu2P=P-P(tBu)2)M(PEt3)Cl] (M=Ni, Pd)
PublicationtBu2P-PLi-P(tBu)2*2THF reaguje z [(Et3P)2MCl2] (M = Ni, Pd) dając odpowiednio [(1,2-h-tBu2P=P-P(tBu)2)Ni(PEt3)Cl] i [(1,2-h-tBu2P=P-P(tBu)2)Pd(PEt3)Cl]. Związek tBu2P-PLi-P(tBu)2 utlenia się i ligand tBu2P-P-P(tBu)2 przyjmuje w produktach strukturę bocznie związanego kationu z krótkim wiązaniem P-P. Reakcja ze związkami platyny nie dała oczekiwanych produktów.
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THYMUS, Thymus - Male, 56 - Tissue image [10060730015611401]
Open Research DataThis is the histopathological image of THYMUS tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Physical properties of the uranium ternary compounds U3Bi4M3 (M=Ni,Rh)
PublicationW pracy dyskutowany jest wzrost kryształów i właściwości fizyczne dwóch, nowych, izostrukturalnych związków U3Bi4Ni3 i U3Bi4Rh3. Pierwszy z nich jest nie-metalem, w drugim obserwowany jest tzw. ferromagnetyczny kwantowy punkt krytyczny.
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Crystal structure and physical properties of Mg6Cu16Si7-typeM6Ni16Si7, for M = Mg, Sc, Ti, Nb, and Ta
PublicationW pracy dyskutowana jest synteza i struktura krystalograficzna, określona poprzez proszkową dyfrakcję rentgenowską, dla pięciu związków M6Ni16Si7, gdzie M = Mg, Sc, Ti, Nb, and Ta. Wszystkie te związki krystalizują w strukturze typu Mg6Cu16Si7.
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catena-Poly[[(diethyl ether-kO)lithium(I)]-m-1,1,3,3-tetraisopropyltriphosphane-kP2: k2P1,P3-lithium(I)-m-1,1,3,3-tetraisopropyltriphosphane-k2P1,P3:kP2]
PublicationTytułowy związek został otrzymany jako produkt uboczny w reakcji [(Et2PhP)2PtCl2] z iPr2P-P(SiMe3)Li. Jest to drugi znany polimer koordynacyjny w grupie soli litowych trifosfanów. Strukturę związku wyznaczono za pomocą rentgenowskiej analizy strukturalnej.
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Nontoxic multinodular goitre - Male, 56 - Tissue image [10060730015613901]
Open Research DataThis is the histopathological image of THYROID GLAND tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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OTHER AND ILL-DEFINED SITES, Thoracic wall, NOS - Male, 56 - Tissue image [10060730015617081]
Open Research DataThis is the histopathological image of OTHER AND ILL-DEFINED SITES tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015618931]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [1006073001561401]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015618801]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015614521]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015613101]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015613181]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015617941]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [1006073001561131]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015615771]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015611581]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Myocarditis, unspecified - Male, 56 - Tissue image [10060730015613241]
Open Research DataThis is the histopathological image of HEART, MEDIASTINUM, AND PLEURA tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015613931]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Pulmonary oedema - Male, 56 - Tissue image [10060730015612461]
Open Research DataThis is the histopathological image of BRONCHUS AND LUNG tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Myocarditis, unspecified - Male, 56 - Tissue image [1006073001561871]
Open Research DataThis is the histopathological image of HEART, MEDIASTINUM, AND PLEURA tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.
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Cardiogenic shock - Male, 56 - Tissue image [1006073001561491]
Open Research DataThis is the histopathological image of KIDNEY tissue sample obtained in Medical University Gdańsk and deposited in ZMDL-GUMED. The sample image was taken using: Pannoramic 250 3DHistech slide scanner (20x magnification) and saved to DICOM format.