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1
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Trastuzumab-dendrimer-fluorine drug delivery system

100%
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
331-341
EN
Breast cancer is the most frequently occurring cancer in women worldwide with more than one million new cases diagnosed each year. The objective of this study was to develop a Trastuzumab-dendrimer-fluorine drug delivery system by covalent attachment of Trastuzumab to a fluorinated PAMAM-G5 dendrimer. The Trastuzumab-dendrimer-fluorine drug delivery system was used to treat MCF-7 with Her-2 overexpression. The use of PAMAM-G5, which bears 128 primary amine surface groups, enables covalent attachment of both antibody and fluorinated functional groups for enhancement of cellular uptake. Thus, Trastuzumab was covalently attached to fluorinated PAMAM-G5 dendrimers and used as a vehicle for drug delivery to three dimensional (3D) cultured cells. The efficiency of Trastuzumab-dendrimer-fluorine drug delivery system binding to Her-2 receptors was measured by cell viability. The Trastuzumab-dendrimer-fluorine drug delivery system was found to have a higher efficiency in the treatment of Her-2 overexpressing MCF-7 cells than Trastuzumab alone. The incorporation of 19F by addition of heptafluorobutyric acid anhydride (HFAA) to PAMAM-G5 increased lipophilicity and hydrophobicity of drug delivery system.
2
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Evaluation of MR relaxation times following trastuzumab treatment of breast cancer cells in a 3D bioreactor

51%
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
|
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.
3
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Trastuzumab Efficacy Quantified by Fluorine-19 Magnetic Resonance Imaging

51%
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.
4
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The potential of Fluorine 19F in in Targeted Therapy

51%
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.
5
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MRI as a potential tool for monitoring of therapeutic monoclonal antibody distribution in cancer patients

51%
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.
6
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Selected applications of fluorinated MR contrast agents and fluorine-containing drugs in medicine

51%
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.
7
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Contrast-enhanced Magnetic Resonance Imaging of lung cell cultures

45%
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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Applications of cytisine extraction and detection in biological materials for clinical medicine

33%
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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