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Search results for: cell death
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Cell Death Discovery
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Journal of Cell Death
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Genes regulating programmed cell death are significantly upregulated in porcine immature oocytes
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Perturbation of cellular functions by topoisomerase II inhibitors: all roads lead to cell death?
PublicationPraca przeglądowa opisuje jakie funkcje mogą ulec zahamowaniu/zmianie pod wpływem działania inhibitorów topoizomerazy typu II w komórkach nowotworowych. W szczególności dyskutujemy jakie zmiany w szlakach sygnalizacji wewnątrzkomórkowej mogą prowadzić do zahamowania wzrostu oraz indukcji różnych rodzajów śmierci komórkowej i czy rodzaj śmierci komórkowej może decydować o skuteczności leków przeciwnowotoworowych, które hamują aktywność...
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The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model
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Modulation of G2 arrest enhances cell death induced by the antitumor 1-nit-roacridine derivative, Nitracrine
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Antitumour imidazoacridone C-1311 induces cell death by mitotic catastrophe in human colon carcinoma cells
PublicationW przedstawionych badaniach określano mechanizm śmierci komórkowej indukowanej przez imidazoakrydon C-1311 (Symadex) w komórkach HT-29 ludzkiego raka jelita grubego, które wykazywały szczególną wrażliwość na ten związek w eksperymentalnych modelach in vitro i in vivo. Przy stężeniu odpowiadającemu dawce IC99, związek powodował zahamowanie progresji cyklu komórkowej w fazie S po czym następował blok w fazie G2. Po czasach 48-96...
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Geldanamycin-Induced Osteosarcoma Cell Death Is Associated with Hyperacetylation and Loss of Mitochondrial Pool of Heat Shock Protein 60 (Hsp60)
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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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Aberration of the enzymatic activity of Fhit tumor suppressor protein enhances cancer cell death upon photodynamic therapy similarly to that driven by wild-type Fhit
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New antitumor unsymmetrical bisacridines derivatives affect c-myc and K-Ras level leading to cell death and accelerated senescence in human lung and colon cancer cells
PublicationUnsymmetrical bisacridines (UAs) are new antitumor derivatives patented in Europe (EP 3070078 B1) and USA (US 10202349 B2). In their structure they consist previously synthesized in our Department drugs: C-1311 and C-1748. Importantly, UAs exhibit different properties than their monomer components. They do not intercalate to dsDNA, but interacts with quadruplex DNA. G-quadruplex structures are present in promoter regions of oncogenes,...
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CELL DEATH AND DIFFERENTIATION
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Cell Death and Disease
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Pro-death signaling of cytoprotective heat shock factor 1: upregulation of NOXA leading to apoptosis in heat-sensitive cells
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Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers
PublicationMultidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes,...
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Ewa Augustin dr hab.
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Chloroacridine derivatives as potential anticancer agents which may act as tricarboxylic acid cycle enzyme inhibitors
PublicationThe chloroacridines affect biological forms of melanoma in different ways. Amelanotic (Ab) melanoma (with inhibited melanogenesis and higher malignancy) was particularly sensitive to the action of the chloroacridines. The Ab melanoma cells died through apoptosis and through death without caspase activation. Diminished activity of TAC enzymes was noticed among Ab melanoma cells together with ATP/NAD depletion, especially in the...
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Novel chalcone-derived pyrazoles as potential therapeutic agents for the treatment of non-small cell lung cancer
PublicationLung cancer is considered to account for approximately one-fifth of all malignant tumor-related deaths worldwide and is therefore one of the most lethal malignancies. Pyrazole scaffold possesses a wide range of biological and pharmacological activities, which play important roles in medicinal chemistry. The present study reports the synthesis and in vitro biological characterization of nine pyrazoles derived from chalcones as potential...
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Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s-like pathology in mouse and fly APP overexpression models
PublicationThe proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer’s disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models. We developed...
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Novel therapeutic compound acridine–retrotuftsin action on biological forms of melanoma and neuroblastoma
PublicationPURPOSE: As a continuation of our search for anticancer agents, we have synthesized a new acridine-retrotuftsin analog HClx9-[Arg(NO2)-Pro-Lys-Thr-OCH3]-1-nitroacridine (named ART) and have evaluated its activity against melanoma and neuroblastoma lines. Both tumors develop from cells (melanocytes, neurons) of neuroectodermal origin, and both are tumors with high heterogeneity and unsatisfactory susceptibility to chemotherapies....
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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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Therapeutic intervention by the simultaneous inhibition of DNA repair and type I or type II DNA topoisomerases: one strategy, many outcomes
PublicationMany anticancer drugs reduce the integrity of DNA, forming strand breaks. This can cause mutations and cancer or cell death if the lesions are not repaired. Interestingly, DNA repair-deficient cancer cells (e.g., those with BRCA1/2 mutations) have been shown to exhibit increased sensitivity to chemotherapy. Based on this observation, a new therapeutic approach termed 'synthetic lethality' has been developed, in which radiation...
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The influence of Nigella sativa essential oil on proliferation, activation, and apoptosis of human T lymphocytes in vitro
PublicationIn previous work, we tested the immunomodulatory effect of Nigella sativa (NS) fatty oil. Our results demonstrated that unrefined, obtained by cold pressing black cumin seed oil inhibited lymphocytes’ proliferation and induced their apoptosis in a dose-dependent manner. In this study, we examined the immunomodulatory properties of essential oil (EO) obtained from the NS seeds by hydrodistillation and its two main constituents:...
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H2AX phosphorylation, its role in DNA damage response and cancer therapy
PublicationDouble-strand breaks (DSBs) are the most deleterious DNA lesions, which, if left unrepaired, may have severe consequences for cell survival, as they lead to chromosome aberrations, genomic instability, or cell death. Various physical, chemical, and biological factors are involved in DSB induction. Cells respond to DNA damage by activating the so-called DNA damage response (DDR), a complex molecular mechanism developed to detect...
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Biochemical, Structural Analysis, and Docking Studies of Spiropyrazoline Derivatives
PublicationIn this study, we evaluated the antiproliferative potential, DNA damage, crystal struc‐ tures, and docking calculation of two spiropyrazoline derivatives. The main focus of the research was to evaluate the antiproliferative potential of synthesized compounds towards eight cancer cell lines. Compound I demonstrated promising antiproliferative properties, especially toward the HL60 cell line, for which IC50 was equal to 9.4 μM/L....
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Triazoloacridone C-1305 impairs XBP1 splicing by acting as a potential IRE1α endoribonuclease inhibitor
PublicationInositol requiring enzyme 1 alpha (IRE1α) is one of three signaling sensors in the unfolding protein response (UPR) that alleviates endoplasmic reticulum (ER) stress in cells and functions to promote cell survival. During conditions of irrevocable stress, proapoptotic gene expression is induced to promote cell death. One of the three signaling stressors, IRE1α is an serine/threonine-protein kinase/endoribonuclease (RNase) that...
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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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Study of the anticancer potential of Cd complexes of selenazoyl-hydrazones and their sulfur isosters
PublicationThe biological activity of Cd compounds has been investigated scarce since Cd has been recognized as a human carcinogen. However, the toxicity of cadmium is comparable to the toxicity of noble metals such as Pt and Pd. The paradigm of metal toxicity has been challenged suggesting that metal toxicity is not a constant property, yet it depends on many factors like the presence of appropriate ligands. Studies on anticancer activity...
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Antitumor DNA-Damaging C-1748 is a New Inhibitor of Autophagy that Triggers Apoptosis in Human Pancreatic Cancer Cell Lines
PublicationDespite the enormous progress that has been made over the past decades in diagnosis, treatment and prevention of many types of tumors, survival rates in pancreatic cancer still remain poor. Pancreatic cancer is one of the most malignant and chemoresistant tumors and the profound mechanism supporting these phenomena is the constitutively activated prosurvival autophagy. The antitumor 1-nitroacridine derivative C-1748 belongs to...
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From tryptophan to novel mitochondria-disruptive agent, synthesis and biological evaluation of 1,2,3,6-tetrasubstituted carbazoles
PublicationMitochondrial targeting plays an important role in anticancer therapy. The Mn(III)-promoted cyclization of 5- (1H-indol-3-yl)-3-oxopentanoic acid allow to obtain novel substituted carbazole derivatives that can act as mitochondria-disruptive agents. The starting materials used for the synthesis of these new aminocarbazoles are oxopentanoate derivatives of tryptophan. The scope and limitation of this method of synthesis are determined...
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The Influence of Antitumor Unsymmetrical Bisacridines on 3D Cancer Spheroids Growth and Viability
PublicationThe culture of 3D spheroids is a promising tool in drug development and testing. Recently, we synthesized a new group of compounds, unsymmetrical bisacridines (UAs), which exhibit high cytotoxicity against various human cell lines and antitumor potency against several xenografts. Here, we describe the ability of four UAs—C-2028, C-2041, C-2045, and C-2053—to influence the growth of HCT116 and H460 spheres and the viability of HCT116...
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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024313501]
Open Research DataThis is the histopathological image of COLON 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024314901]
Open Research DataThis is the histopathological image of STOMACH 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024319561]
Open Research DataThis is the histopathological image of LIVER AND INTRAHEPATIC BILE DUCTS 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024311971]
Open Research DataThis is the histopathological image of ADRENAL 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024313201]
Open Research DataThis is the histopathological image of BRAIN 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024319951]
Open Research DataThis is the histopathological image of LIVER AND INTRAHEPATIC BILE DUCTS 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024315261]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [314063002431991]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024315951]
Open Research DataThis is the histopathological image of SMALL INTESTINE 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024316621]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024314991]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [314063002431621]
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.
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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024317491]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024317921]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024311601]
Open Research DataThis is the histopathological image of BRAIN 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024315421]
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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024319141]
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.
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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024316011]
Open Research DataThis is the histopathological image of BRAIN 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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Fetal death of unspecified cause - Male, 0 - Tissue image [3140630024312461]
Open Research DataThis is the histopathological image of BRAIN 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.