730 research outputs found
PEO1-OR cells acquire resistance through subclonal en-richment of BRCA2 secondary mutations that restore functional full-length protein - whole-exome sequencing.
No full textWhole-exome sequencing (WES) was performed with the Agilent SureSelect Human All Exon V8 Kit (Agilent Technologies, Santa Clara, CA, USA[ŁB1] ) on PEO1 and PEO1-OR cell line tumor samples. Paired-end (2 × 150 bp) next-generation sequencing was performed on a NovaSeq 6000 Sequencing System (Illumina, San Diego, CA, USA[ŁB2] ) to obtain a mean coverage of more than 100×. Briefly, freshly thawed and recovered cells from passage 1 were seeded in 100 mm dishes (5 × 105 cells in 8 mL of culture medium) and cultured for four days (37 °C, 5% CO2) until reaching 80% confluency. Afterward, cells were harvested by trypsinization, and genomic DNA was isolated and purified using GenElute Mammalian Genomic DNA Miniprep Kits (Sigma-Aldrich) according to the manufacturer’s instructions. The quality, integrity, and purity of isolated DNA were evaluated using agarose gel electrophoresis and a spectrophotometer. Genomic DNA was stored in an ultrapure, molecular biology grade Tris-HCl solution (10 mM, pH 8.0) at –80 °C for a week until downstream analysis.Raw sequence data were aligned and annotated for individual samples to a reference sequence of the human genome (GRCh38). Duplicate reads were excluded from downstream analysis. Next, variants were called utilizing GATK’s Haplotype Caller and interpreted using Qiagen Clinical Insight Interpret Translational (QCI-IT) software. Briefly, SnpEff 4.3 prediction toolbox was used to annotate called variants and predict their effects on protein structure and function (gain of function, loss of function, normal function, or change of function). False-positive variants were filtered out using GATK’s Variant Filtration module.Thereafter, we restricted our analysis to the interpretation of single-nucleotide variants (SNVs) and short insertions and deletions (indels) in genes encoding studied proteins, i.e., p53 (TP53, NM_000546.6), ATR (ATR, NM_001184.4), CHK1 (CHEK1, NM_001114121.2), PARP1 (PARP1, NM_001618.4), PARG (PARG, NM_003631.5), BRCA1 (BRCA1, NM_007294.4), BRCA2 (BRCA2, NM_000059.4), MDR1 (ABCB1, NM_001348945.2), 53BP1 (TP53BP1, NM_005657.4), H2AX (H2AX, NM_002105.3), and RAD51 (RAD51, NM_002875.5), using the somatic workflow of QCI-IT software. To improve the high confidence of detected variants, we kept high-quality calls that passed upstream pipeline filtering and all of the confidence filters (call quality ≥30, genotype quality ≥30, and read depth ≥10). To keep only rare variants, any variant with a maximum population frequency >5% in the gnomAD database was classified as benign and excluded from further interpretation (unless previously established as a pathogenic common variant), according to recommendations. High-quality variants were classified based on an automatically computed evidence-based categorization considering their pathogenicity (pathogenic, likely pathogenic, uncertain significance, likely benign, benign) and actionability in terms of therapeutic, diagnostic, and prognostic clinical significance (tier I—strong, tier II—potential, tier III—unknown, tier IV—benign or likely benign) according to the guidelines. </p
Simultaneous blockade of PARP and ATR/CHK1 pathway is more effective in killing ovarian cancer cell lines than drugs alone
No full textThe combination of olaparib with anticancer agents that disrupt HRR by targeting ataxia telangiectasia and Rad3-related protein (ATR) or checkpoint kinase 1 (CHK1) may be an effective strategy to reverse ovarian cancer resistance to olaparib. Here, we evaluated the effect of olaparib, the ATR inhibitor AZD6738, and the CHK1 inhibitor MK8776 alone and in combination on cell survival, colony formation, DNA damage and apoptotic changes in BRCA2 mutated (PEO-1) and HRR-proficient BRCA wild-type (SKOV-3 and OV-90) cells. Combined treatment caused the accumulation of DNA DSBs. Synergistic effects were weaker when olaparib was combined with CHK1i and occurred regardless of the BRCA2 status of tumor cells. Because PARPi increases the reliance on ATR/CHK1 for genome stability, the combination of PARPi with ATR inhibition suppressed ovarian cancer cell growth independently of the efficacy of HRR.</p
MK-8776 and Olaparib combination demonstrates lack of adverse effects on liver tissues in ovarian cancer PDX model
No full textHistopathological Analysis of Liver Tissues in olaparib-resistant PDX model treated with PARPi alone or in combination with a CHK1 inhibitorObjectives:To evaluate the effectiveness and side effects of the drugs in patient-derived xenograft (PDX) models, we examined whether ovarian tumor cells metastasized to the liver after therapy. Methods: Olaparib-resistant PDX tumors were treated with PARPi alone or in combination with a CHK1 inhibitor for histopathological analysis. The levels of Ki-67 (a proliferation marker) and CHK1 kinase phosphorylation at Ser345 were assessed. Hematoxilin and eosin staining (H&E) staining was used to differentiate and visualize the detailed structure of tissue components. Results: An Hematoxilin and eosin (H&E) based evaluation of the liver tissue from mice with olaparib-resistant ovarian cancer revealed no evidence of metastasis to the liver. Ki-67 and pCHK staining showed no changes in liver tissue, indicating the absence of metastases and confirming that the treatment did not induce hepatotoxic effects.The dataset includes microscopic images from IHC and H&E staining of liver tissues.Folder and file list: Folder 1. Hematoxilin and eosin staining of liver tissue images (png format) and staining procedure description (odt format).Folder 2. Immunohistochemistry staining of liver tissue images_Ki67 marker (png format) and preparation of liver sections and immunohistochemistry staining procedure description (odt format).Folder 3. Immunohistochemistry staining of liver tissue images_pCHK1 marker (png format) and preparation of liver sections and immunohistochemistry staining procedure description (odt format).Readme file. Data&file overview, methodological information, environmental/experimental conditions, abbreviations used to describe images </p
Aneta Rogalska-Marasińska, Edukacja międzykulturowa na rzecz zrównoważonego rozwoju. Edukacja, teorie kształcenia i wychowania. Łódź 2017
No full textRecenzja publikacji:Aneta Rogalska-Marasińska, Edukacja międzykulturowa na rzecz zrównoważonego rozwoju. Edukacja, teorie kształcenia i wychowania. Łódź 2017
Recenzja: Zbigniew Dąbrowski, Anna Marchewka, Aneta Teległów (red.), "Hematologia sportowa", Wydawnictwo Lekarskie PZWL, Warszawa 2022
No full textThe academic textbook entitled Hematologia sportowa [Sports Haematology] was published by Wydawnictwo Lekarskie PZWL in Warsaw. It had its premiere on November 23, 2021 and was released in printed form (paperback, 244 pages, ISBN number: 978-83-200-6573-2). The publication was co-financed under the programme of the Minister of Science and Higher Education entitled ‘Regional Initiative of Excellence’ in years 2019–2022, project number 022/RID/2018/19.The handbook is a result or a collaborative effort under the scientific editorship by Prof. Zbigniew Dąbrowski, Prof. Anna Marchewka, and Assoc. Prof. Aneta Teległów (University of Physical Culture in Krakow). The author contributors include 10 academics from the University of Physical Culture in Krakow and 13 academics or physicians representing other research institutions.Podręcznik akademicki opatrzony tytułem Hematologia sportowa został wydany przez Wydawnictwo Lekarskie PZWL w Warszawie. Swoją premierę miał 23 listopada 2021 r. i został wydany w wersji drukowanej (miękka oprawa, liczy 244 strony; numer ISBN: 978-83-200-6573-2). Publikacja była współfinansowana przez Ministra Nauki i Szkolnictwa Wyższego w ramach programu pod nazwą „Regionalna Inicjatywa Doskonałości” w latach 2019–2022, nr projektu 022/RID/2018/19.Podręcznik akademicki jest pracą zespołową. Został przygotowany pod redakcją naukową: prof. dr hab. Zbigniewa Dąbrowskiego, prof. dr hab. Anny Marchewki i dr hab. Anety Teległów, prof. AKF z Akademii Kultury Fizycznej im. Bronisława Czecha w Krakowie, a zespół Autorów tworzy 10 nauczycieli akademickich z Akademii Kultury Fizycznej im. Bronisława Czecha w Krakowie oraz 13 nauczycieli akademickich i lekarzy reprezentujących inne jednostki naukowe
Edukacja międzykulturowa na rzecz zrównoważonego rozwoju
No full textInspiracją do powstania książki była potrzeba podzielenia się z Czytelnikiem obserwacjami oraz naukową refleksją nad współczesną wielokulturową rzeczywistością społeczną i współtworzącym ją człowiekiem. Autorka łączy prezentowaną problematykę z postulatem naprawy relacji międzyludzkich i międzykulturowych poprzez zgodę na powszechną realizację idei zrównoważonego rozwoju, którą postrzega jako niezbędny dziś cel aktywności społeczności globalnej. Sugeruje wykorzystanie edukacji międzykulturowej, dostrzegając w niej najbardziej uzasadnione narzędzie wychowawcze, aby wielokulturowa społeczność globu dokonała zmiany swoich postaw i wybrała odbudowę podstawowych środowisk życia ludzi (przyrodniczego, kulturowego, społecznego i gospodarczego) na zasadach harmonii i współbycia, z odrzuceniem narracji zysku, rabunkowej gospodarki, przymusu rywalizacji oraz niechęci wobec drugiego człowieka. Znaczącym i nowatorskim spojrzeniem na wyzwania zrównoważonego rozwoju jest odwołanie się do obszaru kultury, który jest jednym z głównych, a zarazem najczęściej pomijanych filarów koncepcji zrównoważenia.Udostępnienie publikacji Wydawnictwa Uniwersytetu Łódzkiego finansowane w ramach projektu „Doskonałość naukowa kluczem do doskonałości kształcenia”. Projekt realizowany jest ze środków Europejskiego Funduszu Społecznego w ramach Programu Operacyjnego Wiedza Edukacja Rozwój; nr umowy: POWER.03.05.00-00-Z092/17-00
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Book Review: Pisarstwo naukowe: między rzemiosłem a sztuką By Krystyna Duraj-Nowakowa (Sosnowiec: Oficyna Wydawnicza „Humanitas”, 2015), pp. 356
No full textAI-assisted tech scouting for carbon capture at Tiroler Rohre : author: Aneta Mertová BA.
No full textIndustries face increasing pressure to cut carbon emissions, making carbon capture technologies essential for sustainability. Yet, the fast-evolving landscape complicates selecting suitable solutions for specific industrial needs. This study explores how AI-assisted technology scouting can streamline this process for Tiroler Rohre, a company aiming to reduce its environmental impact. Using tools like Microsoft Copilot and ChatGPT, the research shows AI can enhance the speed and accuracy of identifying and evaluating carbon capture options. By analyzing patents, literature, and reports, AI helps assess technologies based on feasibility, scalability, cost, and environmental impact. The study highlights three high-priority solutions: Carbon-Binding Cement Compositions, Amine-Based Post-Combustion Capture, and Pressure Swing Adsorption. While AI offers a scalable, systematic approach to innovation, human oversight is needed to address issues like hallucinations and data reliability. This research offers a practical framework for integrating AI into sustainable tech selection and supports informed decision-making for carbon reduction.Masterarbeit University Innsbruck 202
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