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Search results for: TRICHOBLASTIC TUMOUR
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Molecular modeling and evaluation of novel dibenzopyrrole derivatives as telomerase inhibitors and potential drug for cancer therapy
PublicationDuring previous years, many studies on synthesis, as well as on anti-tumor, anti-inflammatory and anti-bacterial activities of the pyrazole derivatives have been described. Certain pyrazole derivatives exhibit important pharmacological activities and have proved to be useful template in drug research. Considering importance of pyrazole template, in current work the series of novel inhibitors were designed by replacing central...
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Diminshed toxicity of C-1748, 4-methyl-9-hydroxyethylamino-1-nitroacridine, compared with its demethyl analog, C-857, corresponds to its resistance to metabolism in HepG2 cells
PublicationThe narrow "therapeutic window" of anti-tumour therapy may be the result of drug metabolism leading to the activation or detoxification of antitumour agents. The aim of this work is to examine (i) whether the diminished toxicity of a potent antitumour drug, C-1748, 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine, compared with its 4-demethyl analogue, C-857, results from the differences between the metabolic pathways for the...
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Improved finite element method for flow, heat and solute transport of Prandtl liquid via heated plate
PublicationIn the current study, a vertical, 3D-heated plate is used to replicate the generation of heat energy and concentration into Prandtl liquid. We discuss how Dufour and Soret theories relate to the equations for concentration and energy. In order to see how efectively particles, interact with heat and a solvent, hybrid nanoparticles are used. It does away with the phenomena of viscous dissipation and changing magnetic felds. The motivation...
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Electrochemical simulation of metabolic reduction and conjugation reactions of unsymmetrical bisacridine antitumor agents, C-2028 and C-2053
PublicationElectrochemistry (EC) coupled with analysis techniques such as liquid chromatography (LC) and mass spectrometry (MS) has been developed as a powerful tool for drug metabolism simulation. The application of EC in metabolic studies is particularly favourable due to the low matrix contribution compared to in vitro or in vivo biological models. In this paper, the EC(/LC)/MS system was applied to simulate phase I metabolism of the representative...
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A strong preference for the TA/TA dinucleotide step discovered for an acridine-based, potent antitumor dsDNA intercalator, C-1305: NMR-driven structural and sequence-specificity studies
PublicationTriazoloacridinone C-1305, a potent antitumor agent recommended for Phase I clinical trials, exhibits high activity towards a wide range of experimental colon carcinomas, in many cases associated with complete tumor regression. C-1305 is a well-established dsDNA intercalator, yet no information on its mode of binding into DNA is available to date. Herein, we present the NMR-driven and MD-refined reconstruction of the 3D structures...
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Selective Cytostatic and Cytotoxic Anticancer Effects of Bisfunctional Agents: A Strategy for the Design of DNA Binding Agents
PublicationVarious agents have been synthesized and proved useful for the National Cancer Institute's anticancer testing as potential new drugs, but most agents suffer side effects from their limited selectivity against cancer cells over healthy ones. Therefore, this paper attempts to describe drugs in terms of the level of tumor cell selectivity which they possess to define the features of mols. that are essential for useful cytotoxicity....
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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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Receptor for advanced glycation end‐products: Biological significance and imaging applications
PublicationThe receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory...
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Diamond Nanofilm Normalizes Proliferation and Metabolism in Liver Cancer Cells
PublicationPurpose: Surgical resection of hepatocellular carcinoma can be associated with recurrence resulting from the degeneration of residual volume of the liver. The objective was to assess the possibility of using a biocompatible nanofilm, made of a colloid of diamond nanoparticles (nfND), to fill the side after tumour resection and optimize its contact with proliferating liver cells, minimizing their cancerous transformation. Methods:...
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Actions of a nitric oxide donor on prostaglandin production and angiogenic activity in the equine endometrium
PublicationNitric oxide (NO) plays an important role in prostaglandin secretion and angiogenesis in the reproductive system. In the present study, the roles of the NO donor spermine NONOate and tumour necrosis factor-alpha (TNF; as a positive control) in prostaglandin production and angiogenic activity of equine endometria during the oestrous cycle were evaluated. In addition, the correlation between NO production...
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Assestment of the anti-cancer activity of the copper complexes with imidazole and pivalato ligands
PublicationDespite the development of science and technology progress so far there have not been found effective drugs for cancer. Many coordination compounds were investigated due to their antitumor potential. The most known cis-diamminedichloroplatinum(II) is used as anti-cancer therapeutic agent. The copper complexes are the coordination compounds possessing anti-tumour properties. Their capability to kill cancer cells is mainly linked...
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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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Nanomaterials for photothermal and photodynamic cancer therapy
PublicationIn recent years, the role of optically sensitive nanomaterials has become powerful moieties in therapeutic techniques and has become particularly emphasized. Currently, by the extraordinary development of nanomaterials in different fields of medicine, they have found new applications. Phototherapy modalities, such as photothermal therapy (PTT) by toxic heat generation and photodynamic therapy (PDT) by reactive oxygen species, are...
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Advanced Sensor for Non-Invasive Breast Cancer and Brain Cancer Diagnosis Using Antenna Array with Metamaterial-Based AMC
PublicationMicrowave imaging techniques can identify abnormal cells in early development stages. This study introduces a microstrip patch antenna coupled with artificial magnetic conductor (AMC) to realize improved sensor for non-invasive (early-stage) breast cancer and brain cancer diagnosis. The frequency selectivity of the proposed antenna has been increased by the presence of AMC by creating an additional resonance at 2.276 GHz associated...
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Metabolism of antitumour agent 1-nitroacridine derivative, C-1748 in pancreatic cancer cell lines
PublicationPancreatic cancer has the highest mortality rate of all major cancers because of limited treatment options. Surgical removal of the tumour is possible only in its early stage, nevertheless the asymptomatic development very often makes unable an accurate diagnose. In the case of metastatic pancreatic cancer only chemotherapy, mainly with gemcitabine, can be offered to patients. However, common resistance towards gemcitabine imposes...
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Similarities and differences in d6 low-spin ruthenium, rhodium and iridium half-sandwich complexes: synthesis, structure, cytotoxicity and interaction with biological targets
PublicationIn this paper, we discussed the similarities and diferences in d6 low-spin half-sandwich ruthenium, rhodium and iridium complexes containing 2,2′-biimidazole (H2biim). Three new complexes, {[RuCl(H2biim)(η6 -p-cymene)]PF6}2·H2O (1), [(η5 - Cp)RhCl(H2biim)]PF6 (2), and [(η5 -Cp)IrCl(H2biim)]PF6 (3), were fully characterized by CHN, X-ray difraction analysis, UV–Vis, FTIR, and 1 H, 13C and 15N NMR spectroscopies. The complexes exhibit...
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Phosphoroorganic Metal Complexes in Therapeutics
PublicationThe present mini-review highlights recent developments on antitumor activity of metal-based therapeutics which have been a subject of researches for the last few decades. In 1965, Rosenberg found that during an electrolysis on platinum electrodes a complex of Pt is generated which inhibited to a great extent a binary fission in Escherichia coli bacteria. This discovery started a new chapter in medicinal chemistry and the interesting...
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The potential interaction of environmental pollutants and circadian rhythm regulations that may cause leukemia
PublicationTumor suppressor genes are highly affected during the development of leukemia, including circadian clock genes. Circadian rhythms constitute an evolutionary molecular machinery involving many genes, such as BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, REV-ERBa, and RORA, for tracking time and optimizing daily life during day-night cycles and seasonal changes. For circulating blood cells many of these genes coordinate their proliferation,...
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imPlatelet classifier: image‐converted RNA biomarker profiles enable blood‐based cancer diagnostics
PublicationLiquid biopsies offer a minimally invasive sample collection, outperforming traditional biopsies employed for cancer evaluation. The widely used material is blood, which is the source of tumor-educated platelets. Here, we developed the imPlatelet classifier, which converts RNA-sequenced platelet data into images in which each pixel corresponds to the expression level of a certain gene. Biological knowledge from the Kyoto Encyclopedia...
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Dominant Pathways of Adenosyl Radical-Induced DNA Damage Revealed by QM/MM Metadynamics
PublicationBrominated nucleobases sensitize double stranded DNA to hydrated electrons, one of the dominant genotoxic species produced in hypoxic cancer cells during radiotherapy. Such radiosensitizers can therefore be administered locally to enhance treatment efficiency within the solid tumor while protecting the neighboring tissue. When a solvated electron attaches to 8-bromoadenosine, a potential sensitizer, the dissociation of bromide...
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CYP3A4-dependent cellular response does not relate to CYP3A4-catalysed metabolites of C-1748 and C-1305 acridine antitumor agents in HepG2 cells
PublicationHigh CYP3A4 expression sensitizes tumor cells to certain antitumor agents while for others it can lower their therapeutic ef fi cacy. We have elucidated the in fl uence of CYP3A4 overexpression on the cellular response induced by antitumor acridine derivatives, C-1305 and C-1748, in two hepatocellular carcinoma (HepG2) cell lines, Hep3A4 stably transfected with CYP3A4 isoenzyme, and HepC34 expressing empty vector. The compounds...
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Novel 2-alkythio-4-chloro-N-[imino(heteroaryl)methyl]benzenesulfonamide Derivatives: Synthesis, Molecular Structure, Anticancer Activity and Metabolic Stability
PublicationA series of novel 2-alkythio-4-chloro-N-[imino-(heteroaryl)methyl]benzenesulfonamide derivatives, 8–24, were synthesized in the reaction of the N-(benzenesulfonyl)cyanamide potassium salts 1–7 with the appropriate mercaptoheterocycles. All the synthesized compounds were evaluated for their anticancer activity in HeLa, HCT-116 and MCF-7 cell lines. The most promising compounds, 11–13, molecular hybrids containing benzenesulfonamide...
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Investigations of Energy Conversion and Surface Effect for Laser-Illuminated Gold Nanorod Platforms
PublicationAchieving a quick temperature increase is a burning issue for biophysical applications, like germ inactivation and tumor ablation, and for energy performances, like solar collectors and steam generators. Based on the plasmon resonance phenomenon, noble metallic nanoparticles have emerged as promising weapons due to their very high biocompatibility, optical properties, and high surface-to-volume ratio, increasing energy conversion...
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CHEMOTHERAPY-MEDIATED COMPLICATIONS OF WOUND HEALING. AN UNDERSTUDIED SIDE EFFECT
PublicationSignificance: Chemotherapy is a primary method to treat cancer, but while cytotoxic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types, including dermal cells and macrophages involved in wound healing, which often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent advances: Despite its...
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Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
PublicationThe molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the...
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Platelet RNA Sequencing Data Through the Lens of Machine Learning
PublicationLiquid biopsies offer minimally invasive diagnosis and monitoring of cancer disease. This biosource is often analyzed using sequencing, which generates highly complex data that can be used using machine learning tools. Nevertheless, validating the clinical applications of such methods is challenging. It requires: (a) using data from many patients; (b) verifying potential bias concerning sample collection; and (c) adding interpretability...
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Comparison of 2D and 3D culture models in the studies of the biological response induced by unsymmetrical bisacridines in cancer cells
PublicationMulticellular tumor spheroids are a good tool for testing new anticancer drugs, including those that may target cancer stem cells (CSCs), responsible for cancer progression, metastasis, and recurrence. Therefore, following the initial evaluation of the impact of antitumor unsymmetrical bisacridines (UAs) on lung and colon cancer cells using traditional monolayer cultures, I extended my investigations and applied the spherical model....
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Optical properties of the chemotherapy drugs used in the central nervous system lymphoma therapy: monitoring drug delivery
PublicationOur aim is to optically monitor the delivery of the chemotherapy drugs for brain tumours, particularly used in the central nervous system (CNS) lymphoma therapy. In vivo monitoring would help to optimize the treatment and avoiding unnecessary medications. Moreover, it would be beneficial to be able to measure which of the multi-regimen drugs actually do penetrate and how well into the brain tissue. There exist several potential...
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Subarachnoid Space: New Tricks by an Old Dog
PublicationPurpose: The purpose of the study was to: (1) evaluate the subarachnoid space (SAS) width and pial artery pulsation in both hemispheres, and (2) directly compare magnetic resonance imaging (MRI) to near-infrared transillumination/backscattering sounding (NIR-T/BSS) measurements of SAS width changes in healthy volunteers.Methods: The study was performed on three separate groups of volunteers, consisting in total of 62 subjects (33...
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Impact of Investments and R&D Costs in Renewable Energy Technologies on Companies’ Profitability Indicators: Assessment and Forecast
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New method to monitor changes in the subarachnoid width and pial artery pulsation for physiological and clinical research
PublicationThere are several medical conditions associated with brain oedema such as traumatic brain injury, intoxication or tumors. Brain edema and related brain parenchyma expansion may lead to compression and subsequent injury of several brain structures. So far, the only method enabling detection and monitoring of the progress a cerebral oedema in a patient, has been monitoring of intracranial pressure (ICP) with a pressure probe inserted...
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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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Phospholipids as potential prevention factor in carcinogenesis
PublicationPhospholipids are a group of complex lipids, which can be used in cancer chemoprevention. Glicerophospholipids are composed of fatty acids esterified to a glycerol backbone, a phosphate group and a hydrophilic residue such as: cho- line, ethanoloamine, serine or inositol. In the sn-2 position of glicerophospholipid usually there are unsaturated fatty acids, i.e. linolenic acid, while in the sn-1 position more typi- cal are saturated...
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The role of glucuronidation in drug resistance
PublicationThe final therapeutic effect of a drug candidate, which is directed to a specific molecular target strongly depends on its absorption, distribution, metabolism and excretion (ADME). The disruption of at least one element of ADME may result in serious drug resistance. In this work we described the role of one element of this resistance: phase II metabolism with UDP-glucuronosyltransferases (UGTs). UGT function is the transformation...
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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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A significance of multi slip condition for inclined MHD nano-fluid flow with non linear thermal radiations, Dufuor and Sorrot, and chemically reactive bio-convection effect
PublicationThe aim of this research is to discuss the significance of slip conditions for magnetized nanofluid flow with the impact of nonlinear thermal radiations, activation energy, inclined MHD, sorrot and dufour, and gyrotactic micro motile organisms over continuous stretching of a two-dimensional sheet. The governing equations emerge in the form of partial differential equations. Since the resultant governing differential equations...
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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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Novel insights into conjugation of antitumor-active unsymmetrical bisacridine C-2028 with glutathione: characteristics of non-enzymatic and glutathione S-transferase-mediated reactions
PublicationUnsymmetrical bisacridines (UAs) are a novel potent class of antitumor-active therapeutics. A significant route of phase II drug metabolism is conjugation with glutathione (GSH), which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes. The aim of this work was to investigate the GSH-mediated metabolic pathway of a representative UA, C 2028. GSH supplemented incubations of C-2028 with rat, but not with human, liver...
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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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Adipokine and cytokine levels in patients with adrenocortical cancer, subclinical Cushing's syndrome and healthy controls
PublicationIntroduction In recent years researchers have focused at hormonal activity in Cushing’s syndrome (CS) in connection with metabolic disorders and the role of adipokines and cytokines secreted by the adipose tissue. The aim of the study was to investigate levels of adipokines and cytokines in patients with: subclinical CS (SCS) – in relation to hormonal parameters of hypercortisolemia, and, adrenocortical cancer (ACC). Materials...
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Mechanism-based inactivation of human cytochrome P450 1A2 and 3A4 isoenzymes by antitumor triazoloacridinone C-1305.
Publication5-Dimethylaminopropylamino-8-hydroxytriazoloacridinone, C-1305, is a promising antitumor therapeutic agent with high activity against several experimental tumors. It was determined to be a potent and selective inhibitor of liver microsomal and human recombinant cytochrome P450 (CYP) 1A2 and 3A4 isoenzymes. Therefore, C-1305 might modulate the effectiveness of other drugs used in multidrug therapy. The objective of this study was...
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Modelling charge transfer processes in C2+ -tetrahydrofuran collision for ion-induced radiation damage in DNA building blocks
PublicationInvestigations of collision-induced processes involving carbon ions and molecules of biological interest in particular DNA building blocks, are crucial to model the effect of radiation on cells in order to improve medical treatments for cancer therapy. Using carbon ions appears to be one of the most efficient ways to increase biological effectiveness to damage cancerous cells by irradiating deep-seated tumors. Therefore, interest...
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PARP inhibition potentiates the cytotoxic activity of C-1305, a selective inhibitor of topoisomerase II, in human BRCA1-positive breast cancer cells
PublicationTwo cellular proteins encoded by the breast and ovarian cancer type 1 susceptibility (BRCA1 and BRCA2) tumor suppressor genes are essential for DNA integrity and the maintenance of genomic stability.Approximately 5-10% of breast and ovarian cancers result from inherited alterations or mutations in these genes.Remarkably, BRCA1/BRCA2-deficient cells are hypersensitive to selective inhibition of poly(ADPribose) polymerase 1 (PARP-1),...
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Zastosowanie technik dwuwymiarowych w analizie frakcji lotnej i oznaczaniu związków bioaktywynych owoców jagody kamczackiej
PublicationDotychczasowe doniesienia literaturowe wskazują, że owoce strefy borealnej, do których należy popularna w Polsce aronia, są źródłem cennych składników odżywczych i prozdrowotnych. Podobnie jagoda kamczacka, należąca do tej grupy owoców, może stanowić źródło substancji istotnych dla ludzkiej diety. Jednakże aktualny stan wiedzy o składzie chemicznym owoców jagody kamczackiej ogranicza się głównie do informacji dotyczących całkowitej...
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Nanoparticles: Taking a Unique Position in Medicine
PublicationThe human nature of curiosity, wonder, and ingenuity date back to the age of humankind. In parallel with our history of civilization, interest in scientific approaches to unravel mechanisms underlying natural phenomena has been developing. Recent years have witnessed unprecedented growth in research in the area of pharmaceuticals and medicine. The optimism that nanotechnology (NT) applied to medicine and drugs is taking serious...
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In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot−β−cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers
PublicationTraditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot−β−cyclodextrin−folic acid (QD−β−CD−FA) platform for targeted and selected delivery of C−2028 unsymmetrical bisacridine in cancer therapy.Herein, we report an initial...
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In vitro enzyme kinetics and NMR-based product elucidation for glutathione S-conjugation of the anticancer unsymmetrical bisacridine C-2028 in liver microsomes and cytosol: major role of glutathione S-transferase M1-1 isoenzyme
PublicationThis work is the next step in studying the interplay between C-2028 (anticancer-active unsymmetrical bisacridine developed in our group) and the glutathione S-transferase/glutathione (GST/GSH) system. Here, we analyzed the concentration- and pH-dependent GSH conjugation of C-2028 in rat liver microsomes and cytosol. We also applied three recombinant human GST isoenzymes, which altered expression was found in various tumors. The...
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Analysis of Factors Influencing the Prices of Tourist Offers
PublicationTourism is a significant branch of many world economies. Many factors influence the volume of tourist traffic and the prices of trips. There are factors that clearly affect tourism, such as COVID-19. The paper describes the methods of machine learning and process mining that allow for assessing the impact of various factors (micro, mezzo and macro) on the prices of tourist offers. The methods were used on large sets of real data...
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Aktywności stymulujące refleksję w nauczaniu języka pisanego w wirtualnej klasie
PublicationThe paper aims to show how to engage students attending an online language course in various activities which by stimulating reflection enhance the learning process and result in better learning outcomes. By blending cognitivist, constructivist, constructionist and behavioural ideas, course developers and tutors can produce materials and use methods which satisfy the varied needs of adults who want to improve their writing skills....
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Activation Energy and Inclination Magnetic Dipole Influences on Carreau Nanofluid Flowing via Cylindrical Channel with an Infinite Shearing Rate
PublicationThe infinite shear viscosity model of Carreau fluid characterizes the attitude of fluid flow at a very high/very low shear rate. This model has the capacity for interpretation of fluid at both extreme levels, and an inclined magnetic dipole in fluid mechanics has its valuable applications such as magnetic drug engineering, cold treatments to destroy tumors, drug targeting, bio preservation, cryosurgery, astrophysics, reaction kinetics,...