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Advancements in targeted cancer therapy. Role of nanotechnology in enhancing drug delivery systems

Szechyńska Joanna, Rak Michalina, Szostecki Rafał

Inżynieria Materiałowa

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2024

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Vol. 45, nr 3

18--25

EN

Cancer, characterized by abnormal cell proliferation, continues to pose a significant challenge for researchers. Current methodologies do not ensure complete remission, frequently resulting in toxicity and suboptimal outcomes. Drug delivery systems (DDS) present a promising avenue for targeted therapy, with the goal of enhancing efficacy while minimizing side effects. Nanotechnology, especially through the utilization of nanoparticle-based drugs, is emerging as a pivotal strategy in oncology, enabling precise delivery of drugs to tumour sites. This review examines the landscape of contemporary anticancer drug delivery systems, emphasizing the crucial role of nanocarriers in enhancing therapeutic efficacy.

PL

Rak, charakteryzujący się nieprawidłową proliferacją komórek, w dalszym ciągu stanowi istotne wyzwanie dla badaczy. Obecne metodologie nie zapewniają całkowitej remisji, co często skutkuje toksycznością i suboptymalnymi wynikami leczenia. Systemy dostarczania leków (DDS) stanowią obiecującą drogę terapii celowanej, której celem jest zwiększenie skuteczności przy jednoczesnej minimalizacji skutków ubocznych. Nanotechnologia, zwłaszcza poprzez wykorzystanie leków na bazie nanocząstek, staje się kluczową strategią w onkologii, umożliwiającą precyzyjne dostarczanie leków do miejsc guza. W tym przeglądzie zbadano krajobraz współczesnych systemów dostarczania leków przeciwnowotworowych, podkreślając kluczową rolę nanonośników w zwiększaniu skuteczności terapeutycznej.

2

Wykorzystanie enzymów w diagnostyce medycznej

Gruba Natalia

Wiadomości Chemiczne

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2023

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[Z] 77, 1-2

75--96

EN

Each tissue has its own specific enzyme profile. Therefore, the detection of changes in the level of certain enzymes in disease states allows conclusions about the location and type of pathological changes occurring in the body. Only a few (out of several hundred) tissue enzymes are used in routine diagnostics - diagnostics of diseases of the liver, pancreas, skeletal muscles and heart muscle. In practice, this test consists in measuring the activity or determining the level of enzyme protein in body fluids. In this article, the characteristics of a few selected enzymes applicable in clinical practice will be presented.

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Narzędzia chemiczne do badania enzymów proteolitycznych przy użyciu cytometrii masowej

Groborz Katarzyna

Wiadomości Chemiczne

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2022

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[Z] 76, 11-12

864-880

EN

Mass cytometry is one of the newest and most high-throughput technologies that allows for the investigation of complex biological systems at single cell level. It relies on the use of stable metal isotopes as labels of specific cell markers and therefore, allows for simultaneous analysis of more than 40 parameters at single cell level. In order to fully explore the potential of mass cytometry, researchers are trying to develop new experimental setups based on the application of pure metal isotopes in biological studies. The incorporation of antibodies into mass cytometry setups, while extremely selective and well-validated, limits the analysis as it shows the whole protein pool present in the cell. In our group, we developed new technology that allows for the identification of active forms of proteins-the ones that actively participate in cell signaling pathways. Activity-based probes are the most valuable tools for enzyme activity profiling and for years now they have been in the center of the method called Activity-Based Protein Profiling. Classic activity-based probes consist of three parts: a warhead (electrophilic binding group that covalently modifies enzyme active site), linker (specific peptide sequence or non-specific carbon chain) and the fluorescent tag that allows for enzyme detection and localization inside the cell. Spectral properties of commercially available fluorophores allow for the detection of up to dozen different cell parameters, with the use of various techniques such as confocal microscopy or flow cytometry. To increase the number of analyzed parameters, we designed activity-based probes that possess DOTA chelating moiety that is able to trap one metal atom per one probe. The combination of mass cytometry with highly selective activity-based probes allowed for the development of new technology that grants the possibility of multiparametric analysis of complex biological samples such as blood or cancer tissue. The new type of activity-based probes (so-called TOF-probes) incorporate various inhibitor scaffolds designed with HyCoSuL technology (Hybrid Combinatorial Substrate Libraries). These compounds possess a variety of unnatural amino acids in their structures, which significantly increases their selectivity toward proteases of interest.

4

Ostatnie doniesienia na temat nanocząstek złota jako biomateriału w stomatologii i medycynie

Sadlik Julia, Szechyńska Joanna, Grzywacz Oliwia, Słota Dagmara, Piętak Karina, Florkiewicz Wioletta

Inżynieria Materiałowa

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2022

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Vol. 43, nr 3

14--19

PL

W ostatnich latach nanotechnologia znacząco rozwinęła się jako dziedzina nauki badająca obiekty o rozmiarach nanometrycznych. Każdego roku pojawia się coraz więcej doniesień i kolejnych koncepcji wykorzystujących różne rodzaje nanomateriałów, głównie w dziedzinie biomedycyny. W tym kontekście szczególnie interesujące są nanocząstki złota cieszące się rosnącym zainteresowaniem naukowców przede wszystkim ze względu na swoje unikalne właściwości optyczne i chemiczne. W przeglądzie skupiono się na ostatnich doniesieniach dotyczących wykorzystania nanocząstek złota, na omówieniu metod ich syntezy oraz właściwościach.

EN

In recent years, nanotechnology has significantly developed as a scientific field that studies nanometer-sized objects. Every year an increasing number of reports and new concepts using different types of nanomaterials appear, mainly in the biomedical field. In this context, gold nanoparticles are of particular interest; they are of growing interest to researchers mostly due to their unique optical as well as chemical properties. The following review focuses on recent reports on the use of gold nanoparticles, furthermore discussing the synthesis methods and their properties.

5

Towards high sensitivity and high-resolution PET scanners: imaging-guided proton therapy and total body imaging

Lang Karol

Bio-Algorithms and Med-Systems

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2022

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Vol. 18, no. 1

96--106

EN

Quantitative imaging (i.e., providing not just an image but also the related data) guidance in proton radiation therapy to achieve and monitor the precision of planned radiation energy deposition field in-vivo (a.k.a. proton range verification) is one of the most underinvested aspects of radiation cancer treatment despite that it may dramatically enhance the treatment accuracy and lower the exposure related toxicity improving the entire outcome of cancer therapy. In this article, we briefly describe the effort of the TPPT Consortium (a collaborative effort of groups from the University of Texas and Portugal) on building a time-of-flight positronemission-tomography (PET) scanner to be used in preclinical studies for proton therapy at MD Anderson Proton Center in Houston. We also discuss some related ideas towards improving and expanding the use of PET detectors, including the total body imaging.

6

Wizualizacja enzymów proteolitycznych za pomocą sond chemicznych oraz cytometrii masowej

Groborz Katarzyna, Poręba Marcin

Wiadomości Chemiczne

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2021

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[Z] 75, 11-12

1171--1191

EN

Proteolytic enzymes, also known as peptidases or proteases, are protein catalysts that are primarily responsible for the hydrolysis of a peptide (amide) bond in peptide and protein substrates. By selective hydrolysis of selected substrates, these enzymes control many physiologically important processes including programmed cell death, blood coagulation cascade, protein maturation, fibrinolysis and many others. On the other hand, however, the imbalance in proteases activity leads to the development of diseases, including cancer, neurodegenerative diseases and coronary diseases etc.. In recent decades there has been great progress in studying the biological functions of many proteolytic enzymes. These observations were made possible through the use of various research techniques including genomics, epigenomics and proteomics. However, a major limitation of these techniques is the lack of information about the exact catalytic activity of the enzymes. For this reason, chemical probes are the most convenient toll for functional investigation of proteolytic enzymes. According to the generally accepted convention, chemical probes are compounds that can detect the catalytic activity of proteolytic enzymes. In general, chemical-based probes (activity-based probes, ABPs) consist of three main components: (1) a reactive binding group that binds permanently to the enzyme active site, (2) a recognition sequence (usually a peptide), which is responsible for the selective binding of a given probe to an individual enzyme or group of enzymes, and (3) a tag, mainly a fluorophore, enabling for detection of the probe-enzyme complex. However, the current limitation of ABPs is that only up to four enzymes can be detected and visualized in parallel, which significantly impedes their application for multi-parametric analysis. To date, the detection of proteases with the use of ABPs was limited to individual enzymes being investigated one by one, thus the obtained picture was far from being complete. In this review we describe the development of a new type of enzyme ABPs, so called TOF-probes that are compatible with mass cytometry format. The application of metal isotopes instead of fluorophores, makes possible to significantly increase the number of enzymes, which can be simultaneously visualized using chemical probes. Mass cytometry is a revolutionary technology that adopts atomic mass spectrometry into flow cytometry applications. The excellence of this method is that each metal isotope (mostly from lanthanides) has its own peak on mass spectrum, which eliminates the problem of signal overlap, thus allows for monitoring of more than 40 parameters at single cell level.

7

Magnetic nanoparticles for cancer cells capture

Karewicz Anna, Machowska Adrianna, Karnas Karolina, Dulińska-Litewka Joanna, Kapusta Czesław

Engineering of Biomaterials

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2021

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Vol. 24, no. 163

22

8

Mathematical modeling of the neutrophil production process supported by administration of glycoprotein

Mika Barbara, Pelka Magdalena, Tkacz Ewaryst

Biocybernetics and Biomedical Engineering

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2021

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Vol. 41, no. 1

45--63

EN

Drugs administered in chemotherapy influence the patient's hematopoietic system. The side effects of chemotherapy can force changes in both the dose of drugs and the schedule of their administration, which in turn may adversely affect the patient's health. During chemotherapy treatment, there is a necessity to continuously monitor basic blood parameters, including the number of neutrophils and blood platelets, responsible for the patient's immunity. The aim of this paper is to study the behavior of the hematopoietic system, during chemotherapy, by means of a modified mathematical model of neutrophil production. We conducted simulations for children from 1–15 years old, suffering from neuroblastoma, who are undergoing chemotherapy treatment with Topotecan (TPT). The proposed model provides an effective tool for signaling the moment when the number of mature neutrophils, circulating in the blood, drops below the critical level, that is, 500 cells/mL. Such a nadir persisting over time may result in severe neutropenia and consequently require a halt or change to the established treatment schedule. In addition, we analyzed the process of neutrophil production during chemotherapy, supported by the application of glycoprotein as a growth factor of stem cells.

9

Positronium as a biomarker of hypoxia

Moskal Paweł, Stępień Ewa Ł.

Bio-Algorithms and Med-Systems

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2021

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Vol. 17, no. 4

311--319

EN

In this review article, we present arguments demonstrating that the advent of high sensitivity total-body PET systems and the invention of the method of positronium imaging, open realistic perspectives for the application of positronium as a biomarker for in-vivo assessment of the degree of hypoxia. Hypoxia is a state or condition, in which the availability of oxygen is not sufficient to support physiological processes in tissue and organs. Positronium is a metastable atom formed from electron and positron which is copiously produced in the intramolecular spaces in the living organisms undergoing positron emission tomography (PET). Properties of positronium, such as e.g., lifetime, depend on the size of intramolecular spaces and the concentration in them of oxygen molecules. Therefore, information on the partial pressure of oxygen (pO2) in the tissue may be derived from the positronium lifetime measurement. The partial pressure of oxygen differs between healthy and cancer tissues in the range from 10 to 50 mmHg. Such differences of pO2 result in the change of ortho-positronium lifetime e.g., in water by about 2–7 ps. Thus, the application of positronium as a biomarker of hypoxia requires the determination of the mean positronium lifetime with the resolution in the order of 2 ps. We argue that such resolution is in principle achievable for organ-wise positronium imaging with the total-body PET systems.

10

Znaczenie nowoczesnej diagnostyki molekularnej w terapii przeciwnowotworowej

Mazur Bogdan, Żydowicz Grzegorz

Laboratorium Medyczne

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2020

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nr 2-3

72--75

PL

W ostatnim dziesięcioleciu w Polsce zapadalność na choroby nowotworowe wzrosła o prawie 28%, przy niezmiennym rozkładzie najliczniej występujących nowotworów. Liczba zgonów związanych z rakiem wzrosła znacząco mniej (7%). Przedstawiono wybór akceptowanych terapii celowanych, wskazując na potrzebę multidyscyplinarnego podejścia do diagnostyki i planowania terapii. Metody osiągnięcia skrócenia oczekiwania na podjęcie skutecznej terapii, na podstawie dostępnego piśmiennictwa, upatruje się w uproszczeniu i uporządkowaniu procedur przepływu informacji oraz wyboru najprostszych, najkrótszych, a jednocześnie pewnych metod diagnostyki molekularnej.

EN

During the last decade, the incidence rate of cancer diseases in Poland has increased by almost 28%, while the distribution of the most frequent neoplasms has remained unchanged. In this period, an increase in cancer-related deaths has been significantly lower (7%). This paper presents commonly accepted modern targeted therapies, indicating the need for a multidisciplinary approach to proper diagnostics and therapy planning. Based on the available literature it can be concluded, that the simplification of procedures, organising the flow of data and the selection of the simplest, shortest and most reliable molecular diagnostic methods are the best ways to reduce waiting time for treatment.

11

Częstość myślenia o chorobie nowotworowej – na przykładzie mieszkańców województwa podkarpackiego

Jarmakowicz Paulina

Inżynier i Fizyk Medyczny

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2020

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Vol. 9, nr 4

283--287

PL

Przeprowadzono ankietę w 316-osobowej, losowo wybranej grupie mieszkańców województwa podkarpackiego. Miała na celu określenie częstości myślenia o możliwości zachorowania na chorobę nowotworową przez respondentów oraz osoby im bliskie. Stwierdzono istotne statystycznie zależności w stosunku do płci, wieku, wykształcenia oraz miejsca zamieszkania.

EN

A survey was conducted in a 316-person randomly selected group of inhabitants of the Podkarpackie Voivodeship. It was aimed at determining the frequency of thinking about the possibility of developing cancer by respondents and people close to them. Statistically significant relationships were found in relation to sex, age, education and place of residence.

12

May metallic biomaterials used for orthopedic implants promote cancer processes? : preliminary trasriptomics research on human articular chondrocytes.

Walkowiak-Przybyło Magdalena, Walczyńska Marta, Kamińska Marta, Komorowski Piotr, Walkowiak Bogdan

Engineering of Biomaterials

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2020

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Vol. 23, no. 158 spec. iss.

32

13

May metallic biomaterials used for orthopaedic implants promote carcinogenesis? Preliminary transcriptomic research on human chondrocytes

Walkowiak-Przybyło Magdalena

Engineering of Biomaterials

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2020

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Vol. 23, no. 157

15--19

EN

The aim of this research was to assess the risk of carcinogenesis induced by the metallic materials intended for orthopaedic implants. The report is an analytical summary of changes in the expression of cancer-related genes in human chondrocytes of normal and neoplastic phenotype. Cq values (quantification cycle values) obtained from qRT-PCR reactions (quantitative real-time polymerase chain reactions) were used to count Fc values (fold change values) for each gene. Differences in Fc values obtained for primary and cancer cells grown on the surface of medical steel AISI316L and titanium-aluminum-vanadium alloy Ti6Al4V were then analyzed by t-Student test. The results indicate that for cancer cells grown on the surfaces of both examined materials the fold change greater than 2, usually considered essential, was found for LUM gene involved in sarcoma induction. For FOS gene, also involved in sarcoma induction, the Fc value was also very close to 2 in the primary cells exposed to Ti6Al4V alloy. The remaining observed changes were rather subtle, although they cannot be omitted from further studies because differences in gene expression in primary and tumor cells grown on the same biomaterial were statistically significant in several cases. The compilation of qRT-PCR experiments carried out on primary and cancer cells in parallel allowed to identify possible future contraindications for patients with a genetic predisposition to cancer or with cancer history.

14

Characterization of partially covered self-expandable metallic stents for esophageal cancer treatment: in vivo degradation

Chytrosz Paulina, Gołda-Cępa Monika, Włodarczyk Janusz, Kuzdzal Jarosław, El Fray Mirosław, Kotarba Andrzej

Engineering of Biomaterials

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2020

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Vol. 23, no. 158 spec. iss.

43

15

Nowatorska i wydajna synteza SV119

Bai Xueyan, Li Xiaoyang, Wu Zhiping

Przemysł Chemiczny

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2019

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T. 98, nr 1

122--128

PL

Opracowano nową metodę syntezy związku SV119, syntetycznego małocząsteczkowego ligandu łączącego się z receptorami sigma-2 i odznaczającego się dużym powinowactwem do tych receptorów. Zaletami tej metody są tanie surowce i niewielkie straty półproduktu podczas oczyszczania. Co więcej, redukcję można przeprowadzić wg uproszczonej procedury przy użyciu izopropanolanu glinu, zapewniającego dużą wydajność reakcji (62%). Opracowana metoda syntezy okazała się przydatna do przemysłowej produkcji związku SV119, który następnie poddano ocenie biologicznej i wykorzystano do dalszych badań.

EN

N-(9-(6-Aminohexyl)-9-azabicyclo[3.3.1]nonan-3-yl)-N-(2- methoxy-5-methylphenyl)carbamate hydrochloride (SV119) was synthesized by subsequent reaction of CO(CH₂COOH)₂, pentanedial and PhNH₂·HCl in aq. soln. in presence of AcONa at 0°C, isolation of raw 9-benzyl-9-azabicyclo[ 3.3.1]nonan-3-one, its conversion with Al(O-i-Pr)₃ to 9-benzyl-9-azabicyclo[3.3.1]nonan-3-ol at 110°C for 6 h, and then to 9-benzyl-9-azabicyclo[3.3.1]nonan-3-yl- 2-methoxy-5-methylphenylcarbamate by reaction with 2-methoxy-5-methylphenylisocyanate and SnBu2(OAc)₂ at room temp. The carbamate was converted to 9-azabicyclo[ 3.3.1]nonan-3-yl-2-methoxy-5-methylphenylcarbamate by reacting with ammonium formate on Pd(OH)₂/C under boiling in MeOH/EtOAc soln. and finally to the title compd. by conversion with an N-(6-bromoalkyl)phthalimide and with NH₂NH₂ under reflux in EtOH for 2 h. The total yield of the synthetic was 62%. The structure of all intermediates and final product was confirmed with ¹H-NMR and IR spectra and by elementary anal.

16

A literature review on multimodality molecular imaging nanoprobes for cancer detection

Shahbazi-Gahrouei Daryoush, Moradi Khaniabadi Pegah, Shahbazi-Gahrouei Saghar, Khorasani Amir, Mahmoudi Farshid

Polish Journal of Medical Physics and Engineering

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2019

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Vol. 25, Iss. 2

57--68

EN

Molecular imaging techniques using nanoparticles have significant potential to be widely used for the detection of various types of cancers. Nowadays, there has been an increased focus on developing novel nanoprobes as molecular imaging contrast enhancement agents in nanobiomedicine. The purpose of this review article is to summarize the use of a variety of nanoprobes and their current achievements in accurate cancer imaging and effective treatment. Nanoprobes are rapidly becoming potential tools for cancer diagnosis by using novel molecular imaging modalities such as Ultrasound (US) imaging, Computerized Tomography (CT), Single Photon Emission Tomography (SPECT) and Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI), and Optical Imaging. These imaging modalities may facilitate earlier and more accurate diagnosis and staging the most of cancers.

17

Mechanical and biological assessment of carbon fiber-reinforced PEEK composite materials intended for laryngeal prostheses

Smolka Wojciech, Dworak Michał, Gubernat Maciej, Markowski Jarosław, Błażewicz Marta

Engineering of Biomaterials

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2019

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Vol. 22, no. 153 spec. iss.

62

18

Variable order 3D models of bone remodelling

Valério D., Neto J., Vinga S.

Bulletin of the Polish Academy of Sciences. Technical Sciences

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2019

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Vol. 67, nr 3

501--508

EN

This paper presents simulations of a three-dimensional model of the bone remodelling process. The model consists of a set of variable order partial differential equations, in which the varying order depends on the presence of tumour cells. The simulations are of a two-dimensional bone, to make visualisation simpler. They show that this model corresponds to the known evolution of bone remodelling, and is simpler than integer order models found in the literature.

19

Doksorubicyna i jej kompleksy w terapiach nowotworów

Filipiuk D., Lewandowski W., Świsłocka R., Świderski G.

Przemysł Chemiczny

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2018

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T. 97, nr 12

2173--2179

PL

Przedstawiono przegląd literaturowy na temat wykorzystania doksorubicyny i jej kompleksów z metalami jako leków w terapii nowotworów.

EN

A review, with 67 refs.

20

Natural xenobiotics inducing apoptosis in hepatoma cells: in vitro study

Starosta M., Tyszka-Czochara M., Bukowska-Strakova K., Dołhańczuk-Śródka A.

Proceedings of ECOpole

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2018

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Vol. 12, No. 2

335--343

EN

The term “xenobiotics” refers to substances which are not produced within the human body, but may occur in human environment. Some of biologically active chemicals may be synthesized by plants. Many studies have been conducted with regard to plant secondary metabolites and the beneficial impact of various plant-derived compounds on human health has been demonstrated. Recent research have shown chemopreventive properties of catechins. (+)-catechin ((2R,3S)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-2H-chromene-3,5,7-triol) and (-)-epigallocatechin gallate (EGCG; [(2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)chroman-3-yl] 3,4,5-trihydroxybenzoate) are compounds abundant in daily human nutrition. Growing body of evidence reports pro-apoptotic effects of catechins. Both catechins have been shown to modulate intracellular pathways network in tumor cells thereby regulating signaling cascades, which results in programmed death of cancer cells, apoptosis. Apoptosis is one of the most potent mechanisms to defense against cancer. During apoptosis, the activation of caspases results in biochemical and morphological changes associated with specific changes in cell phenotype. Besides apoptosis, tumor cells may be also eliminated from organism via necrosis, however the latter process may evoke local inflammation, which in turn may result in detrimental effects within the body. Xenobiotics with potential to cause apoptosis of cancer cells may be considered in modern combined anticancer therapies and/or to assist existing treatments.

PL

W środowisku występują substancje obce o charakterze ksenobiotyków, czyli związków chemicznych niesyntetyzowanych w sposób naturalny w ciele człowieka. Wiele takich aktywnych biologicznie związków może być produkowanych przez rośliny. Przeprowadzone dotychczas badania wskazują, że drugorzędowe metabolity roślinne mogą wywierać pozytywny wpływ na zdrowie człowieka. Na przykład wyniki ostatnich obserwacji potwierdziły chemoprewencyjne właściwości katechin. (+)-katechina (ang. (2R,3S)-2-(3,4dihydroxyphenyl)-3,4dihydro-2H-chromene-3,5,7-triol) oraz (-)-galusan epigallokatechiny (ang. EGCG; [(2R,3R)-5,7-dihydroxy-2(3,4,5-trihydroxyphenyl)chroman-3-yl] 3,4,5-trihydroxybenzoate) to związki o charakterze ksenobiotyków występujące w diecie człowieka. Ostatnie odkrycia zwracają uwagę w szczególności na proapoptotyczne właściwości związków z tej grupy. Obydwa wymienione związki chemiczne mogą modyfikować przebieg wewnątrzkomórkowych ścieżek sygnałowych w komórkach nowotworowych. Takie oddziaływanie może uruchamiać kaskadę aktywności prowadzącą do apoptozy, programowanej śmierci komórki neoplastycznej. Apoptoza jest jednym z mechanizmów, które wykorzystuje się w nowoczesnych terapiach przeciwnowotworowych. Apoptozę charakteryzuje szereg zmian w przebiegu procesów biochemicznych i morfologii komórki. Komórki nowotworowe mogą być eliminowane również na drodze nekrozy, jednakże ten typ śmierci komórkowej często prowadzi do lokalnego stanu zapalnego, co jest zjawiskiem niekorzystnym dla organizmu. Drugorzędowe metabolity roślinne, takie jak (+)-katechina i (-)-galusan epigallokatechiny, mogą wykazywać zdolność do wywoływania śmierci apoptotycznej komórek nowotworowych i potencjał ten może być wykorzystywany w nowoczesnych przeciwnowotworowych terapiach kombinowanych lub do wspierania istniejącego leczenia.