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1
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Evaluation of MR relaxation times following trastuzumab treatment of breast cancer cells in a 3D bioreactor

100%
Bartusik-Aebisher D., Aebisher D., Czmil A., Mazur D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 1
35-41
EN
The three dimensional tumor environment can be mimicked with the use of cells cultured within a hollow-fiber bioreactor (HFBR). In this work, magnetic resonance imaging (MRI) was used to monitor changes in relaxation time in breast cancer cells following treatment with Trastuzumab in a HFBR system. Breast cancer cells were inoculated into the HFBR system and cultured over a period of 4 weeks. Relaxation time maps were generated according to MRI techniques in three dimensional (3D) cultures of MCF7/Her2 breast cancer and MCF7/Neo4 control cells. MRI measurements showed a variation in values of spin-lattice (T1) and spin-spin (T2) relaxation times related to cell density. Differences in both values (T1 and T2) were noted between untreated cells and cells treated with trastuzumab in the HFBR device. Additionally, 1H MRI was able to provide information about drug penetration in breast cancer cell culture organized in 3D. In conclusion, MRI in vitro can provide direct, noninvasive visualization of cell density in 3D geometry and cell viability as a function of drug uptake. Both T1 and T2 values were higher for lower cell density and accordingly both values, T1 and T2, were lower for higher cell density.
2
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Trastuzumab Efficacy Quantified by Fluorine-19 Magnetic Resonance Imaging

100%
Bartusik-Aebisher D., Aebisher D., Czmil M. A., Mazur D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 3
495-503
EN
The purpose of this study was to conjugate Trastuzumab with fluorine-bearing PAMAM dendrimer to compare activities in three-dimensional (3D) cultured breast cancer cells with parent Trastuzumab. An in vitro study was performed to determine cellular responses to fluorinated Trastuzumab conjugates by Magnetic Resonance Imaging (MRI). Breast cancer cells were cultured in 3D geometry. Proton (1H) MRI and Fluorine-19 (19F) MRI were used for visualization of cellular locations within a Hollow Fiber Bioreactor (HFBR) device and to monitor the cellular response to treatment. The results of this study confirm that cell growth is significantly decreased following treatment with Trastuzumab conjugates. The use of fluorinated Trastuzumab conjugates decreases breast cancer cell growth in 3D cultures and allows for tracking of drug delivery to cancer cells via 19F.
3
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The potential of Fluorine 19F in in Targeted Therapy

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Bartusik-Aebisher D., Aebisher D., Podgórski R., Leksa N.
Acta Poloniae Pharmaceutica - Drug Research
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2019
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vol. 76
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issue 6
939-943
EN
Fluorine-19 (19F) can provides critical information about the mobility of the drug and drug uptake in cancer tissue when used together with 19F Magnetic Resonance Imaging (19F MRI) in vitro or in vivo. This review is aimed at the current limitations of drugs such as quantitative visualization during treatments of tumor cells. The main rationale about the utility of 19F MRI is visualization of fluorinated drug and fluorine conjugates on the cellular in vitro and in vivo levels.
4
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MRI as a potential tool for monitoring of therapeutic monoclonal antibody distribution in cancer patients

100%
Tabarkiewicz J., Aebisher D., Bartusik-Aebisher D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 3
383-389
EN
Imaging and quantification of MAbs distribution by MRI after administration in vivo can improve patient outcomes, although it is not routinely used in the clinic hence the motivation for development of new MAbs imaging methodologies. Improvements in imaging and quantification of antibody distributions can be made by conjugating MAbs to “hotspot” atoms such as 19F as 19F Currently, research investigating the incorporation of 19F to antibody delivery systems has been limited to trastuzumab perfluorocarbon emulsions and this method has not been extended to other clinically approved antibodies. The methodologies of 19F MRI can improve current limitations of antibody immunotherapy such as quantitative visualization of targeted surface antigens expressed on tumor cells.
5
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Selected applications of fluorinated MR contrast agents and fluorine-containing drugs in medicine

100%
Bartusik-Aebisher D., Bober Z., Aebisher D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 3
403-410
EN
This review aims to present magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) for applications in cellular therapeutics including descriptions of the use of 19F MRI and 19F MRS in drug tracking and visualization. Both MRI and MRS are often used as diagnostic tools in oncology, are non-invasive, and also can be employed for monitoring non-oncological and oncological therapies. Herin, we provide information pertaining to tracking and visualization of fluorinated drug uptake in cancer tissue in vitro, in vivo and ex vivo. The response of tissue to treatment is also discussed.
6
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Congenital adrenal hyperplasia: clinical symptoms and diagnostic methods

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Podgórski R., Aebisher D., Stompor M., Podgórska D., Mazur A.
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2018
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vol. 65
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issue 1
25-33
EN
The aim of this paper is a straightforward presentation of the steroidogenesis process and the most common type of congenital adrenal hyperplasia (CAH) - 21-hydroxylase deficiency - as well as the analytical diagnostic methods that are used to recognize this disease. CAH is a family of common autosomal recessive disorders characterized by impaired adrenal cortisol biosynthesis with associated androgen excess due to a deficiency of one or more enzymes in the steroidogenesis process within the adrenal cortex. The most common and prototypical example of the CAH disorders group (90-95%) is caused by 21-hydroxylase deficiency. Less frequent types of CAH are 11β-hydroxylase deficiency (up to 8% of cases), 17α-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, P450 oxidoreductase deficiency and StAR deficiencies. In the 21-hydroxylase and 11β-hydroxylase deficiency, only adrenal steroidogenesis is affected, whereas a defect in 3β-hydroxysteroid dehydrogenase or 17α-hydroxylase also involves gonadal steroid biosynthesis. Many countries have introduced newborn screening programs based on immunoassays measuring 17-hydroxyprogesterone from blood spots used for other neonatal screening tests which enable faster diagnosis and treatment of CAH. Currently, chromatographic techniques coupled with mass spectrometry are gaining popularity due to an increase in the reliability of the test results.
7
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Contrast-enhanced Magnetic Resonance Imaging of lung cell cultures

88%
Bober Z., Pogoda K., Aebisher D., Tabarkiewcz J., Bartusik-Aebisher D.
Acta Poloniae Pharmaceutica - Drug Research
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2020
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vol. 77
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issue 2
251-258
EN
Lung cancer is one of the most common types of cancer diagnosed, and the development of methods to image diseased lung tissue by MRI is of utmost importance. Contrast-Enhanced Magnetic Resonance Imaging (CE-MRI) was used to noninvasively evaluate spin-spin relaxation time, T1, of lung cell cultures infused with various clinical gadolinium-based contrast media for imaging. In this study we used a clinical 1.5 Tesla scanner and the contrast agents: Omniscan, MultiHance, Gadovist and ProHance. A significant five-fold reduction of T1 relaxation time was obtained.
8
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Synthesis and biological evaluation of 4'-O-acetyl-isoxanthohumol and its analogues as antioxidant and antiproliferative agents

76%
Stompor M., Świtalska M., Podgórski R., Uram Ł., Aebisher D., Wietrzyk J.
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2017
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vol. 64
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issue 3
577-583
EN
Isoxanthohumol (2) and its 4'-O-monoacylated (3) and 7,4'-O-diacetylated (4) derivatives were synthesized and evaluated in vitro for their cytotoxic activity against several cancer cell lines of various origins: MCF-7 (breast), A549 (lung), MESSA (uterine sarcoma), LoVo (colon), drug-resistant human cancer cells (MESSA/DX and LoVo/DX), glioblastoma (U-118 MG), and also towards the non-cancerous cell line MCF-10A (normal breast cells). An antiproliferative assay indicates that 7,4'-di-O-acylisoxanthohumol (4) has similar cytotoxicity to its precursor, isoxanthohumol (2), against selected cell lines (A549, MES-SA, MES-SA/5DX, and U-118 MG). Compound 4 was only slightly more cytotoxic to lung, colon, breast (cancerous and normal) and uterine sarcoma (drug sensitive and drug resistant) cell lines compared to its monoacylated derivative (3). Both acylated isoxanthohumols showed preferential activity against tumor cells (MCF-7) and low cytotoxicity to normal cells (MCF-10A), which suggests selectivity of the acylated isoxanthohumols towards cancer cells. Additionally, the activity of the acylated isoxanthohumols was higher than for 2. To the best of our knowledge this is the first report on bioactivity of monoacylated isoxanthohumol (3) and its ester derivatives as antiproliferative compounds in drug resistant cell cultures. Acylation of 2 decreased the antioxidant activity determined by the DPPH method in the order isoxanthohumol (2) >4'-O-acetylisoxanthohumol (3) >7,4'-di-O-acetylisoxanthohumol (4).
9
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Applications of cytisine extraction and detection in biological materials for clinical medicine

64%
Bartusik-Aebisher D., Aebisher D., Courtney R., Sobczak A., Bober Z., Podgórski R., Kołodziejczyk P., Tutka P.
Acta Poloniae Pharmaceutica - Drug Research
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2019
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vol. 76
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issue 5
797-804
EN
Tobacco use is a leading cause of preventable mortality worldwide. New cost-effective smoking cessation treatments are needed especially in some low-to-middle income countries where smoking rates are rising, and current pharmacotherapy treatments remain cost-prohibitive. Since the 1960’s, cytisine has been used as an effective nicotine substitution agent to aid in smoking cessation albeit limited to a selected few Eastern/Central Europe and Central Asian countries. Cytisine is a biologically active alkaloid of plant origin and is known to be a ligand of nicotinic acetylcholinergic receptors (nAChRs). For several decades, the properties of cytisine have been investigated and reported in the biomedical and pharmaceutical literature. Due to the beneficial impact of cytisine on smoking cessation and its costly multistep synthesis, there is a growing interest in extraction from natural sources as well as in analytical identification and quantification for clinical medicine and forensic toxicology. In this paper, we present several current analytical approaches to cytisine extraction and identification from biological samples of plant and human origin. The development of extraction techniques will allow for the widespread use of the drug in experimental and clinical pharmacology, toxicology and forensic medicine.
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