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Advances in active and passive immunotherapy for Alzheimer’s disease– a short review

100%
Jacek Tabarkiewicz J.
Medical Review
|
2016
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issue 1
93-96
PL
STRESZCZENIE Choroby neurodegeneracyjne m.in. choroba Alzheimera (AD) dotykają rocznie miliony nowych pacjentów na całym świecie. Fakt ten spowodował intensywny rozwój terapii modyfikujących przebieg choroby i mogących mieć zastosowanie w AD. Dane przedkliniczne wykazały zaangażowanie układu immunologicznego w patogenezie choroby Alzheimera. Komórki mikrogleju, komórki prezentujące antygen np. komórki dendrytyczne oraz produkty aktywacji dopełniacza odgrywają aktywną rolę w neurodegeneracji. Z drugiej strony niektóre elementy układu odpornościowego mogą być wykorzystane do eliminacji złogów amyloidowych i innych nieprawidłowości związanych z AD. W związku z tym, metody pasywnej i aktywnej immunoterapii są jednym z najszybciej rozwijających się sposobów terapii choroby Alzheimera. Podawanie przeciwciał lub indukcja odpowiedzi immunologicznej przeciwko β-amyloidowi, α-synukleinie lub białku tau są intensywnie badane. Jest to związane z odkryciem, że białka te mogą być celem dla przeciwciał w przypadku ich ekspresji na błonie komórkowej lub w przestrzeni pozakomórkowej. Także stosowanie innych metod immunoterapii pasywnej (podawanie dożylnych immunoglobulin) i aktywnej (szczepionki na bazie DNA) jest związane z pozytywnymi efektami klinicznymi. Kolejne próby kliniczne prowadzą do rozwóju efektywnych i bezpiecznych metod immunoterapii choroby Alzheimera i innych chorób neurodegeneracyjnych.
EN
Disease-modifying alternatives are intensively developed for the treatment of neurodegenerative disorders, a group of diseases that afflict millions of patients annually. The pre-clinical data shown involvement of immune system in the pathogenesis of Alzheimer’s disease (AD). Microglia cells, antigen presenting cells like dendritic cells and products of complement activation take an active part in neurodegeneration. On the other hand, some components of immune system could be used for elimination of amyloid plaques and another structural abnormalities associated with AD. Because of that, passive and active immunotherapies are one of the most developed approaches in therapy of AD. Vaccination against amyloid-ß, α-synuclein, or tau has been extensively explored, especially as the discovery that these proteins may propagate cell-to-cell and be accessible to antibodies when embedded into the plasma membrane or in the extracellular space. Also other methods of passive (intravenous immunoglobulins) and active (DNA based vaccines) are associated with positive clinical outcome. The clinical development of efficient and safe immunotherapies for Alzheimer ’s disease and other neurodegenerative disorders is a field in constant evolution.
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An overview of the preclinical and clinical studies of the effects of tumor treating fields on malignant glioma cells

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Dorota Bądziul D., Agnieszka Banaś-Ząbczyk A., Jacek Tabarkiewicz J.
European Journal of Clinical and Experimental Medicine
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2017
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issue 2
141-144
EN
Anaplastic astrocytoma (AA, WHO grade III) and glioblastoma multiforme (GBM, WHO grade IV) are malignant tumors of the brain. The average survival time of patients with GMB is approximately one year and two years in the case of anaplastic astrocytoma with standard therapy based on surgical tumor resection followed by chemotherapy or radiotherapy. High invasiveness of gliomas, the ability of rapid division and so-called diffusive infiltration of tumor cells into normal brain tissue, which prevents complete surgical removal, are hallmarks of theses tumors. Therefore, new specific therapies for eliminating cancer cells are needed to treat this tumors. Recently, it has been demonstrated that alternating electric field, also known as tumor treating fields (TTFields) has a unique mechanism of destroying glioma cells. TTFields applies electromagnetic energy frequency-dependent and intensitydependent and disrupts cancer cell replication as they undergo mitosis. Futhermore, TTFields turn out to act comparably to conventional chemotherapeutics, lacking numerous side adverse associated with chemotherapy. The authors provide an up-todate review of the mechanism of action as well as preclinical and clinical data on TTFields.
3
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How genetic predispositions may have impact on injury and success in sport

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Justyna Czarnik-Kwaśniak J., Konrad Kwaśniak K., Jacek Tabarkiewicz J.
European Journal of Clinical and Experimental Medicine
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2018
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issue 4
366-375
EN
Introduction. Studies investigating the determinants of physical endurance were initiated nearly 30 years ago. The research was inspired by the curiosity to find out about the nature of talent for sport and why some athletes are better than others, despite the same or even greater effort in training routine, diet and the supplementation. An attempt was therefore made to determine the genotype of a perfect athlete, but conducted research showed that it is a very difficult task. Although 140 genes were proposed to affect of ideal sportsman fitness, scientists are still far from formulating answers about the nature of physical abilities and genotype. Aim. Our main goal was to review the literature about the selected genes and polymorphisms which are most often investigated in the context in relation to injury in sports. Materials and methods. Analysis of literature from US National Library of Medicine, National Institutes of Health, PubMED, Google Scholar. Results. We review the selected genes and polymorphisms which are most often investigated in the context in relation to injury in sports, we also present the function of genetic variants prevalent in athletes which are able to achieve better physiological adaptation during the training. Conclusions. There are probably more than 140 genes involved in physical performance. Changes in even one nucleotide within the gene (SNP) can improve the body’s adaptation to better physical performance and the frequency of injury to athletes.
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Fibrodysplasia Ossificans Progressiva – a presentation of cases and literature review

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Małgorzata Dąbrowska M., Piotr Dąbrowski P., Jacek Tabarkiewicz J.
European Journal of Clinical and Experimental Medicine
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2019
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issue 2
184-191
EN
Introduction. Fibrodysplasia ossificans progressiva (FOP) is a very rare inherited disease leading to progressive ectopic ossification of muscle and soft tissue and resulting in severe immobilisation and premature death. The mutations in ACVR1 gene that codes the 1A activin receptor which belongs to the family of bone morphogenetic proteins (BMPs) are leading to clinical symptoms. Aim. In this raport we present 3 cases of paediatric FOP patients presenting varied clinical course of disease. Description of the cases. Case 1. A girl, currently 5 years old, was hospitalised for the first time at the age of 10 months with suspicion of a hyperplastic lesion of the left lumbar area. The time period between the first symptom, i.e. subcutaneous oedema, and the correct diagnosis was about 8 months. The symptom with key importance for the diagnosis was congenital deformities of the thumbs and big toes. Case 2. A 6-year-old girl with a congenital hallux valgus in both feet, a small painless nodular lesion in the area of the distal metaphysis of the femur, limiting the flexion of the knee joint, was diagnosed in the third month of life. Case 3. A three-year-old girl was diagnosed with congenital defects i.e. hallux valgus of both feet. The first symptoms of the disease occurred during her 14th month when an oedema of the subcutaneous tissue of the nape area was observed. Conclusion. Until recently, there has been no efficient therapy which could slow down the natural course of the disease and currently the disease is treated as incurable. Of key importance from the perspective of patients is early diagnosis and, more importantly, preventing traumas, surgical procedures, intramuscular injections, sparing dental treatment and ensuring avoidance of airway tract infections.
5

Glycosylation of immune system proteins and its role in autoimmune diseases and cancer

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Anna Trzyna A., Jacek Tabarkiewicz J., Artur Mazur A.
European Journal of Clinical and Experimental Medicine
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2020
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issue 1
32-37
EN
Introduction. Structural glycans have great biological significance and are involved in signaling and cell communication of the immune system. They are attached to proteins and lipids in an enzymatic process called glycosylation where glycosyltransferase and glycosidases bind sugar residues and lead to the formation of bioconjugates. Aim. In this paper we describe the importance of glycosylation in the immune system and its changes in diseases. Material and methods. This review was performed according to systematic literature search of major bibliographic databases. Results. Proper glycosylation ensures the functioning of the organism, however, defects in structural glycans of immune system changes their properties and can lead to disorders and further to autoimmune diseases. It has been also proven that glycosylation of autoimmune system is changed during cancer. In this paper we described types of structural glycans, significance of glycosylation of selected components of the immune system and its modifications in disorders. Conclusions. Knowledge about changes in the glycosylation in diseases is the key to understanding the processes of autoimmune diseases and may allow the development of new treatments in the future.
6
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Chemiluminescence-driven Dye Excitation for Dark Photodynamic Therapy

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Łukasz Ożóg Ł., Jacek Tabarkiewicz J., David Aebisher D.
European Journal of Clinical and Experimental Medicine
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2017
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issue 2
95-98
EN
Photodynamic therapy is a treatment that uses a combination of light-absorbing photosensitizers and dissolved oxygen to kill cancer. One specific limitation of photodynamic therapy is that the visible light used for photosensitizer excitation has a short tissue penetration depth of several millimeters. This limits the application of photodynamic therapy to surface cancers in the absence of a technique to illuminate deeper tissue. Efforts to extend tissue depth to which photodynamic therapy can be applied have been attempted with use of up-conversion and persistent-luminescent nanoparticles that absorb near infrared light and emit visible light for photosensitizer excitation, yet an initial excitation with an external light source is still required. More recently, systems employing chemiluminescence as an excitation energy source designed to bypass the use of external light have been developed and investigated as potential agents that could overcome the problem of achieving photodynamic therapy in deep tissue. We wish to provide an overview of several systems that have been recently reported that employ both radiative and non-radiative chemiluminescent energy transfer for photosensitizer excitation that have been developed in the hope of achieving “dark” photodynamic therapy. This article reviews several of these important new developments in the design of photodynamic therapeutic systems that utilize chemiluminescence.
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19F MRI As a tool for imaging drug delivery to tissue and individual cells

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Zuzanna Bober Z., David Aebisher D., Łukasz Ożóg Ł., Jacek Tabarkiewicz J., Piotr Tutka P., Dorota Bartusik-Aebisher D.
European Journal of Clinical and Experimental Medicine
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2017
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issue 2
99-109
EN
Over the past few decades, magnetic resonance imaging (MRI) has proven to be extremely successful in medical applications. More recently, the biomedical applications of MRI have been gaining more use in the field of clinical pharmacy. In 1977, perfluorocarbon compounds (PFC), which form emulsions that can carry drugs, were analyzed by 19F MRI and emulsified PFC compounds have been investigated as potential blood substitutes since the early 1960s and now a wide variety of PFC compounds are currently available as 19F MRI biomarkers. Molecules with 19F substituents are particularly attractive for use in drug tracking by 19F MRI due to 100% 19F abundance, high 19F MRI sensitivity (0.83 relative to 1H MRI) and an impressively large chemical shift range (400 ppm). Another benefit in the use of 19F MRI is a zero background signal in biological samples due to lack of endogenous fluorine. Therefore, drugs containing fluorine atom have potential for 19F MRI imaging drug delivery to tissue. This article will review recent developments in the use of 19F MRI in imaging drug delivery to tissue and individual cells.
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Optimization of detection of circulating tumor cells by flow cytometry and qRT-PCR

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Katarzyna Pogoda K., Paweł Rybojad P., Inés Ramírez Álvarez I. R., Thusyanthan Mohanathas T., Sarah Hosseini S., Jacek Tabarkiewicz J.
European Journal of Clinical and Experimental Medicine
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2019
|
issue 1
5-11
EN
Introduction. Treatment and diagnostic process in solid tumors like lung cancer are still based on invasive methods such as bronchoscopy, solid biopsy et cetera. One of the less invasive methods is a proposed “liquid biopsy” which is based on capturing of tumor cells circulating in the blood. Aim. The aim of the study was to standardize conditions and to assess the sensitivity of the identification of circulating tumor cells (CTCs) with the use of flow cytometry and qRT-PCR. Material and methods. In the first model of CTCs, cells from the A549 lung cancer cell line were suspended in 1 ml of healthy donors’ blood in 5 spikes increasingly: 0, 10, 50, 100 and 200 and the cells were detected in flow cytometer. In the second model, cells from the A549 and H1975 lung cancer cell lines were used. Spikes were prepared as in the first model, but cells were suspended in 400 µl of healthy donors’ blood and were detected with the use of qRT-PCR. Results. An increasing number of detected cytokeratin positive events from the 1st spike “0” to the last one - “200” was observed by flow cytometry. Median value in the negative control was 0 false positive cells. In tubes from “10” to “200” the median was 5, 43.5, 58 and 78, respectively. Mean sensitivity of flow cytometry was 63.79%. In qRT-PCR, correlation between increasing number of sorted cells in several spikes and the level of mRNA expression for KRT19 gene was not observed. Conclusion. Commonly available methods like flow cytometry and qRT-PCR seem to be attractive solutions for CTCs detection, but they need pre-enrichment procedures and standardization
9
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Expression of heat shock protein 70 in the tissue of patients with laryngeal squamous cell carcinoma

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Aleksandra Barańska A., Aleksandra Maziarz A., Jacek Roliński J., Janusz Klatka J., Katarzyna Dudzińska-Ćwiek K., Jacek Tabarkiewicz J.
European Journal of Clinical and Experimental Medicine
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2019
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issue 1
16-21
EN
Introduction. Laryngeal squamous cell carcinoma (LSCC) is a common type of head and neck malignancy. Because of unsatisfactory results of therapy, development of new strategies for LSCC treatment is needed. It is believed that heat shock protein 70 (HSP70) is involved in pathogenesis of LSCC. Thus, targeting HSP70 seems to be promising strategy for laryngeal cancer treatment. Aim. The aim of the study was to assess the HSP70 concentration in laryngeal squamous cell carcinoma specimens and its correlation with tumor volume and TNM staging. Material and methods. An ELISA method and a Bradford protein assay were used to evaluate the HSP70 concentration in peripheral blood cells, tumor tissue and lymph nodes from the patients suffering from LSCC. Results. We demonstrated that the HSP70 concentration is significantly different between examined compartments. The highest level was observed in peripheral blood, while the lowest was in the lymph nodes. The HSP70 expression was correlated to tumor volume. Conclusion. Our results showed varied expression of HSP70 in tissue from patients with LSCC, but there was no association between HSP70 concentration and TNM staging. Currently, application of HSP70 inhibition as a LSCC treatment could be rather associated with systemic blocking of this molecule than target inhibition in tumor tissue. However, further analysis on a larger group of patients is needed.
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Investigation of pharmaceuticals by nuclear magnetic resonance imaging and spectroscopy

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Zuzanna Bober Z., David Aebisher D., Jacek Tabarkiewicz J., Wiesław Guz W., Piotr Tutka P., Dorota Bartusik-Aebisher D.
European Journal of Clinical and Experimental Medicine
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2017
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issue 2
110-119
EN
Currently, new and easier ways of analyzing pharmaceutical drug forms and drug delivery mechanisms are being sought. Magnetic resonance imaging (MRI) is a non-invasive imaging technique that images drug forms such as tablets, liquids and topicals and drug form behavior in living organisms on both the tissue and cellular scale. The advantages of MRI include noninvasiveness, variable sample capacity and ease of transfer of phantom results to in vitro and in vivo studies. This review concerns the usefulness of clinical MRI that cannot be understated as this technique provides non-invasive and non-destructive insight into the properties of drug delivery systems. The research discussed here concerns the use of magnetic resonance, spectroscopy and chromatography to investigate selected pharmaceuticals and covers work of selecting drugs and antibodies for modification by synthesis for evaluation by MRI. Modifications have been aimed at improving therapeutic efficacy, delivery, and MRI. Modification conditions such as (pH, concentration, temperature, and the influence of other components present in the solutions) will be discussed to understand drug delivery system improvements and the reliability and repeatability of the results obtained. We hope to explore and expand the scope of pharmaceutical imaging with MRI for application in clinical medicine.
11
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Lycopene activity on lung and kidney cancer cells by T2 relaxation time 1 H Magnetic Resonance Imaging in vitro

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Katarzyna Pogoda K., Maria Pucka M., Jacek Tabarkiewicz J., Zuzanna Bober Z., David Aebisher D., Sabina Galiniak S., Dorota Bartusik-Aebisher D.
European Journal of Clinical and Experimental Medicine
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2020
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issue 1
5-9
EN
Introduction. The paper presents the results of a study of cell cultures of lung cancer and kidney cancer using lycopene performed using clinical magnetic resonance imaging. Aim. The aim of the study was to evaluate lycopene activity on tumor cell cultures. Material and methods. For this purpose, MR tests were performed using the technique of determining transverse relaxation. Results. Described here studies demonstrated that lycopene may inhibit the growth of A549 and ACHN cell lines. Conclusion. We determine changes in spin lattice relaxavity T2 to monitor treatment of lung cancer cell line A549 and kidney cancer cell line ACHN cells treatment with lycopene.
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