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Tytuł:
The role of E2F2 in signaling pathways associated with cancer pathogenesis and potential treatment: A review of current studies
Autorzy:
Domańska, Julia
Poboży, Kamil
Domański, Paweł
Fudalej, Marta
Deptała, Andrzej
Badowska-Kozakiewicz, Anna
Powiązania:
https://bibliotekanauki.pl/articles/22792539.pdf
Data publikacji:
2023-07
Wydawca:
Medical Education
Tematy:
E2F2
E2F
cancer
transcription factor
oncology
p53
p21
Opis:
Introduction and objective. E2F transcription factor 2 (E2F2) protein is the transcription factor that plays an important role in tumorigenesis. E2F2 effects the cell cycle, tumor suppressor proteins, and can also be transformed by proteins of small DNA tumor viruses. The objective of the study is to provide a summary of the current knowledge on the neoplastic pathways that involve E2F2. State of knowledge. Numerous studies have demonstrated a role for E2F2 in various signaling pathways. Certain components of these pathways may serve as potential targets for oncological therapy. E2F2 has been shown to be associated with neoplasms of various locations and histological types (breast, colon, gastric, laryngeal, liver, lung, ovarian, pancreatic, and prostate cancers). Conclusions. Further investigations of E2F2 pathways are warranted for a clearer understanding of neoplastic processes and to identify novel pharmacological treatments.
Źródło:
OncoReview; 2023, 13, 2; 58-66
2450-6125
Pojawia się w:
OncoReview
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The Reformation of Turkish Commercial Law within the Process of European Union Candidacy
Autorzy:
Yasan, Mustafa
Powiązania:
https://bibliotekanauki.pl/articles/915234.pdf
Data publikacji:
2020
Wydawca:
Katolicki Uniwersytet Lubelski Jana Pawła II
Tematy:
Turkish commercial law, Turkish Code of Commerce, Turkey EU relations, Turkish company law.
Abuzer Kendigelen, 2016, Türk Ticaret Kanunu Değişiklikler, Yenilikler ve İlk Tespitler, 3. Baskı, İstanbul, Oniki Levha Yayınları. Ali Bozer / Celal Göle, 2018, Kıymetli Evrak Hukuku, 8. Baskı, Ankara, Banka ve Ticaret Hukuku Araştırma Enstitüsü Yayınları. Ali Bozer / Celal Göle, 2018, Ticari İşletme Hukuku, 5. Baskı, Ankara, Banka ve Ticaret Hukuku Araştırma Enstitüsü Yayınları. Alihan Aydın, 2012, Ticari İşletme Kavramı, Unsurları ve Hukuki İşlemlere Konu Olması, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.9-21, İstanbul. Arslan Kaya, 2012, Acentelik ile İlgili Yenilikler, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.53-71, İstanbul. Burak Sertoğlu, 2019, Ticari İşletme Devri, Ankara, Seçkin Yayınevi. Enver Bozkurt / Arif Köktaş, Avrupa Birliği Hukuku, 2018, 7. Baskı, Ankara, Legem Yayıncılık. Erdoğan Moroğlu, 2012, 6102 sayılı Türk Ticaret Kanunu, Değerlendirmeler ve Öneriler, 7. Baskı, İstanbul, Oniki levha Yayınları. Hamdi Yasaman, 2012, Haksız Rekabet, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.33-46, İstanbul. Hikmet Sami Türk, 2005, Tasarı Hakkında Genel Değerlendirme, Türk Ticaret Kanunu Tasarısı, Konferans, p.17-41, Ankara. Mehmet Bahtiyar, 2013, Kıymetli Evrak Hukuku, 11. Bası, İstanbul, Beta Yayınevi. Mehmet Bahtiyar, 2019, Ortaklıklar Hukuku, 13. Bası, İstanbul, Beta Yayınevi. Mehmet Emin Bilge, 1999, Ticaret Sicili, İstanbul, Beta Yayınevi. Mehmet Fatih Arıcı, 2008, Ticari İşletmenin Aktif ve Pasifi ile Devri, İstanbul, Vedat Kitapçılık. Mustafa Çeker, 2013, Ticaret Hukuku, 6. Baskı, Adana, Karahan Kitapevi. Oğuz İmregün, 1996, Kara Ticaret Hukuku Dersleri, 11. Baskı, İstanbul, Filiz Kitapevi. Oruç Hami Şener, 2016, Ticari İşletme Hukuku, Ankara, Seçkin Yayınevi. Oruç Hami Şener, 2017, Limited Ortaklıklar, Ankara, Seçkin Yayınevi. Rıza Ayhan / Mehmet Özdamar / Hayrettin Çağlar, 2012, Ticari İşletme Hukuku, 5. Bası, Ankara, Yetkin Yayınevi. Sıtkı Anlam Altay, 2012, Ticari Kayıtlar ve Defterlerin Tutulmasına İlişkin Hukuki Esaslar ve İsbat Sorunu, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.100-111, İstanbul. Şükrü Yıldız, 2012, Gerçek Kişilerde Tacir Sıfatının Kazanılması, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.21-33, İstanbul. Şükrü Yıldız, 2007, Limited Şirketler Hukuku, İstanbul, Arıkan Kitapevi. Tolga Ayoğlu, 2012, Bağlı ve Bağımsız Tacir Yardımcıları, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.46-53, İstanbul. Ünal Tekinalp, 2005, Tasarının Takdimi, Türk Ticaret Kanunu Tasarısı, Konferans, p.7-17, Ankara. Veliye Yanlı, 2012, Ticaret Sicili, Yeni Türk Ticaret Kanunu’nun Ticari İşletme Hukuku Alanında Getirdiği Yenilikler, p.89-100, İstanbul.
Opis:
The relationship between Turkey and the European Union began in 1959 with Turkey's application for membership. This relationship has survived to this day and in this process negotiations for membership have been frozen. This process contributed directly to Turkish law. This contribution has become more significant, especially since 1999. Turkish Code of Commerce entered into force in 2012, is recognized as a result of Turkey's EU process. By this Code, it is aimed to ensure harmonization between Turkish Commercial Law and EU legislation. For this reason, regulations in the sense of reform were included in TCC. However, the Code has been amended for a total of eighteen times. Sixteen times after the coming into force, two times even before coming into force. More than three hundred articles have been directly affected by these changes. The principles foreseen in the Code have been abandoned because of adopting a populist approach. This situation is accepted as a failure and disappointment for the TCC codification experience.
Źródło:
Review of European and Comparative Law; 2020, 40, 1; 25-43
2545-384X
Pojawia się w:
Review of European and Comparative Law
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
GENTIAN VIOLET: WHAT WE KNOW AND WHAT IS AHEAD OF US
Autorzy:
Dragan, Jędrzej
Michalak, Sylwia S.
Powiązania:
https://bibliotekanauki.pl/articles/895376.pdf
Data publikacji:
2019-06-28
Wydawca:
Polskie Towarzystwo Farmaceutyczne
Tematy:
p53
Crystal Violet
Gentian Violet
fungal infection
bacterial infection
Opis:
At present, the only active substance of Gentian Violet (GV) is methylrosaniline - a triphenylmethane dye of which amino group contains 2 methyl groups. GV can be used to treat uncomplicated bacterial and/or yeast infections, support antibiotic therapy of more severe infections, but also to protect medical equipment against colonization by microorganisms. In the light of recent studies, there are many new possibilities for GV application. It has been shown to be effective in the treatment of viral infections, some chronic skin diseases and oncology. GV can induce apoptosis of tumor cells among others by elevating caspase 8, inhibiting NADPH oxidases, decreasing mitochondrial thioredoxin 2 or inhibiting STAT3/SOX2 axis. Preclinical and in vitro studies have also demonstrated GV efficacy in the treatment of breast cancer, melanoma tumors and cutaneous T-cell lymphoma. There is no unambiguous evidence indicating the toxicity of GV, whereas its safety has been proven by its long history of use, its inclusion in numerous guidelines and its legal trade and distribution with no specific approval requested in many countries around the world. The article gathers the available knowledge about GV and its potential use in the future.
Źródło:
Acta Poloniae Pharmaceutica - Drug Research; 2019, 76, 3; 389-396
0001-6837
2353-5288
Pojawia się w:
Acta Poloniae Pharmaceutica - Drug Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Single stranded-DNA detection: the role of Wip1 in ATR-dependent pathway
Autorzy:
Kurpas, Monika
Jonak, Katarzyna
Puszynski, Krzysztof
Powiązania:
https://bibliotekanauki.pl/articles/747336.pdf
Data publikacji:
2018
Wydawca:
Polskie Towarzystwo Matematyczne
Tematy:
ATR
Wip1
mathematical model
UV
p53
ATR, Wip1, model matematyczny, UV, p53.
Opis:
Obszary pojedynczonciowego DNA (ssDNA) powstaja w komórkachw wyniku ekspozycji na stres na przykład- promieniowanie UVC-lub podczas naprawy podwójnoniciowych pekniec DNA. ATR (ataxia telangiectasia mutated and Rad3-related) jest odpowiedzialne za wykrywanie ssDNA. Niedawno wykazano kluczowa role fosfatazy Wip1, która inaktywuje główne elementy szlaków odpowiedzi na uszkodzenia DNA. Opracowalismy matematyczny model sciezki ATR i połaczylismygo z modelem szlaku supresora nowotworowego p53, odpowiadajacego za aktywacje genów zaangazowanych w reakcje komórki na uszkodzenie materiału genetycznego (naprawe DNA/apoptoze). Co wiecej, dodalismy fosfataze Wip1, jako główny czynnik odpowiedzialny za wyłaczenie sciezek sygnałowych uruchamianych w ramach reakcji na uszkodzenie. Uzyskane wyniki pokazuja, ze dzieki prawidłowo dobranej dawce UVC i wyciszeniu lub zablokowaniu aktywnosci Wip1, mozliwe jest skierowanie komórek nowotworowych na szlak apoptotyczny
Single-stranded DNA (ssDNA) areas arise in cells as a result of exposure to stress agents - like UVC - or during repair of DNA double-strand breaks. ATR(ataxia telangiectasia mutated and Rad3-related) is responsible for detecting ssDNA. Recently, it has been shown that one of the most important components of cellular response to the damage is Wip1 phosphatase, which inactivates main elements of DNA damage response (DDR) pathways. We developed a mathematical model of ATR detector system, connected to p53 tumor suppressor responsible for activation of genes involved in cellular response to the damage (DNA repair/apoptosis). Moreover, we added Wip1 phosphatase, as a main agent responsible for turning o DDR. Our results show that the apoptotic threshold, where more than half of cells die, is equal to 20 J/m2. The threshold shifts when activity of the specied proteins involved in the pathway is blocked or reduced. Moreover with accurate dose of UVC and silenced or blocked Wip1, it may be possible to drive cancer cells to apoptotic pathway.
Źródło:
Mathematica Applicanda; 2018, 46, 1
1730-2668
2299-4009
Pojawia się w:
Mathematica Applicanda
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Strongly Time-Consistent Core in Differential Games with Discrete Distribution of Random Time Horizon
Silnie zgodny w czasie rdze« gry ró»niczkowej z dyskretnym losowym horyzontem
Autorzy:
Malakhova, Anastasiya Pavlovna
Gromova, Ekaterina Victorovna
Powiązania:
https://bibliotekanauki.pl/articles/953387.pdf
Data publikacji:
2018
Wydawca:
Polskie Towarzystwo Matematyczne
Tematy:
differential games
random time horizon
cooperative solution
strong time-consistency
core
discrete distribution
imputation distribution procedure
atr
wip1
model matematyczny
uv
p53
Opis:
In this paper we investigate the problem of strong time-consistency of the core for a particular class of differential games with random time horizon, namely, it is assumed that there exists a set of probabilities of the end of the game at discrete time instants. A condition guaranteeing the strong time consistency of the core is presented.
Źródło:
Mathematica Applicanda; 2018, 46, 2
1730-2668
2299-4009
Pojawia się w:
Mathematica Applicanda
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Immunological and genotoxic effects of occupational exposure to α-cypermethrin pesticide
Autorzy:
El Okda, El-Sayed
Abdel-Hamid, Mona A.
Hamdy, Ahmed M.
Powiązania:
https://bibliotekanauki.pl/articles/2161902.pdf
Data publikacji:
2017-06-19
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
p53
pyrethroids
immunological
genotoxic
cypermethrin
Oxidative stress
Opis:
Objectives The aim of this work has been to find out the occupational oxidative stress, immunological and genotoxic health hazards among α-cypermethrin (CYP) pesticide-exposed workers. Material and Methods A cross-sectional study was performed including 200 workers divided into 3 groups according to the level of exposure: highly exposed group (50 workers), moderately exposed group (50 workers) and unexposed group (100 workers). All workers were subjected to detailed laboratory investigation for gene P53 mutations, immunological parameters as a cluster of differentiation into 3 percentage (CD3%), CD4% and CD8% in addition to peripheral blood total leukocytic and platelet counts that were measured. Spectrophotometer technique was used for detection of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx). Air samples were collected with a High Volume Small Surface Sampler for measurement of α-cypermethrin level. Results A highly exposed group to the α-cypermethrin had lower CD4/CD8 as compared to an unexposed group with statistically significant difference. As regards gene mutation, exons 5a and 6 were more frequent among the highly exposed group as compared to no mutation among moderately exposed and unexposed groups with significant difference. As regards antioxidants; SOD, CAT, GSH and GPx were higher among the unexposed group as compared to the highly and moderately exposed group with statistically significant difference. Significant negative correlation was found between working years and antioxidant parameters. Conclusions Repeated exposure to α-CYP may lead to gene mutations, immunological disturbances and oxidative stress. Strict safety precautions are required not only for workers but also for public users. Int J Occup Med Environ Health 2017;30(4):603–615
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2017, 30, 4; 603-615
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Proinflammatory cytokines (IL-6, IL-18) and apoptotic factors (HP 53, survivin) in patients with alcoholic liver cirrhosis
Autorzy:
Prystupa, Andrzej
Kiciński, Paweł
Sak, Jarosław
Grzybowski, Andrzej
Boguszewska-Czubara, Anna
Toruń-Jurkowska, Anna
Niedziałek, Jarosław
Załuska, Wojciech
Powiązania:
https://bibliotekanauki.pl/articles/972717.pdf
Data publikacji:
2017
Wydawca:
Instytut Medycyny Wsi
Tematy:
survivin
alcoholic liver cirrhosis
proinflammatory cytokines
apoptosis
human protein p53
Opis:
Background. Apoptosis is involved in the pathogenesis of alcoholic liver cirrhosis. Its development can be triggered by an inflammatory process. In the present study, levels of apoptotic factors – survivin human protein p53 (HP 53) and IL-6, IL-18 were determined according to the stage of liver cirrhosis. Material and methods. Seventy patients with alcoholic liver cirrhosis, treated in various hospitals of the Lublin region, Poland were included in the study. Serum levels of IL-6, IL-18, HP53 and survivin were determined by the enzyme-linked immunosorbent assay (ELISA) technique. Results. The serum level of survivin in patients with alcoholic liver cirrhosis was not statistically different from that found in the control group. The level of HP53 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (16.53±22.69 vs. 0.39±1.31 U/ml; p<0.001). Likewise, the level of IL-6 was significantly higher in the group of patients with alcoholic liver cirrhosis compared to the control group (33.83±41.78 vs. 0.88 ± 0.56 pg/ml; p<0.001). Moreover, the level of IL-18 was significantly higher in the group of patients with liver cirrhosis compared to the control group (23.96±31.07 vs. 5.3±8.6 pg/ml; p<0.001). Conclusion. In conclusion, increased serum levels of IL-6 and IL-18 were demonstrated in patients with alcoholic liver cirrhosis. Moreover, the liver cirrhosis patients had elevated levels of HP53, which is a marker of apoptosis. Our results did not demonstrate the correlation between the levels of apoptosis markers (survivin, HP53) and the levels of cytokines (IL-6, IL-18) in the blood serum.
Źródło:
Journal of Pre-Clinical and Clinical Research; 2017, 11, 1; 1-5
1898-2395
Pojawia się w:
Journal of Pre-Clinical and Clinical Research
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The role of the 5 terminal region of p53 mRNA in the p53 gene expression
Autorzy:
Swiatkowska, Agata
Zydowicz, Paulina
Sroka, Joanna
Ciesiołka, Jerzy
Powiązania:
https://bibliotekanauki.pl/articles/1038716.pdf
Data publikacji:
2016
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
p53
transcription
translation
non-coding region
mRNA
IRES
Opis:
The p53 tumour suppressor protein is one of the major factors responsible for cell cycle regulation and protection against cancer development. This is why it is often referred to as "the guardian of the genome". On the other hand, mutations in the p53 gene are connected with more than 50% of tumours of various types. The thirty-six years of extensive research on the p53 gene and its protein products have shown how sophisticated the p53-based cell system control is. An additional level of complexity of the p53 research is connected with at least twelve p53 isoforms which have been identified in the cell. Importantly, disturbance of the p53 isoforms' expression seems to play a key role in tumorigenesis, cell differentiation and cell response to pathogenic bacteria, and RNA and DNA viruses. Expression of various p53 isoforms results from the usage of different transcription promoters, alternative splicing events and translation initiation from alternative AUG codons. The importance of the 5'-terminal regions of different p53 mRNA transcripts in the multi-level regulation of the p53 gene has recently been documented. In this review we focus on the structural features of these regions and their specific role in the p53 translation initiation process.
Źródło:
Acta Biochimica Polonica; 2016, 63, 4; 645-651
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
The effect of phenobarbital on gene expression levels of p53 and DNMT1 in the liver of Wistar rats
Autorzy:
Urbanek-Olejnik, K.
Liszewska, M.
Kostka, G.
Powiązania:
https://bibliotekanauki.pl/articles/874211.pdf
Data publikacji:
2014
Wydawca:
Narodowy Instytut Zdrowia Publicznego. Państwowy Zakład Higieny
Tematy:
phenobarbital
gene expression
animal exposure
rat
p53 gene
Dnmt1 gene
liver
Wistar rat
Opis:
Background. Our previous studies have shown that short-term treatment with phenobarbital (PB) resulted in cytosine methylation of CpG sites on the p53 gene promoter in male Wistar rats’ liver. Furthermore, PB induced DNA-methyltransferases (DNMTs) activity was also demonstrated; being the enzymes that catalyze methyl group transfer to cytosine in CpG dinucleotides. Objective. Since DNA methylation is involved in regulating gene transcription and that DNMT1 is implicated in regulating DNA methylation, this study assessed whether PB-induced hypermethylation of the p53 promoter region was associated with an altered expression of p53 and Dnmt1 genes. Material and methods. Male Wistar rats received PB in three daily oral doses (at 24-h intervals) of 92,8 mg/kg b.w. x day-1. Levels of mRNA for p53 and Dnmt1 and levels of relevant proteins were respectively examined by Real-Time PCR and Western blot analysis. Results. Gene expression analysis revealed that exposure of Wistar rats to PB caused statistically significant alternations in the expression of tested genes. We found that both mRNA and protein expression of p53 was down-regulated, whereas expression of Dnmt1 (both mRNA and protein) was up-regulated after PB treatment. Conclusions. Suppression of p53 mRNA and protein expression, which is probably a result of epigenetic changes, (in particular aberrant p53 promoter hypermethylation), can be associated with tumour promoting activity of phenobarbital.
Wprowadzenie. Nasze wcześniejsze badania wykazały, że krótkoterminowe narażenie szczurów Wistar na fenobarbital (PB) stymulowało metylację cytozyny w badanych sekwencjach rejonu promotorowego genu p53. Ponadto stwierdzono wzrost aktywności metylotransferaz DNA (DNMT), enzymów które katalizują przenoszenie grupy metylowej do cytozyny w dinukleotydach CpG. Cel badań. Z uwagi że metylacja DNA pełni istotną rolę w ekspresji genów, a DNMT1 uczestniczy w regulacji metylacji DNA, w prezentowanych badaniach oceniano czy indukowana PB hipermetylacja rejonu promotorowego genu p53 była związana ze zmianami ekspresji genów p53 i Dnmt1. Materiał i metody. Samce szczurów szczepu Wistar otrzymywały PB w dawce 92,8 mg/kg m.c. x dzień-1, 3-krotnie w odstępach dobowych. Analizę poziomu transkryptów i białek badanych genów przeprowadzano odpowiednio metodą Real- -Time PCR i Western blot. Wyniki. W wyniku oddziaływania PB wykazano obniżoną ekspresję genu p53 i wzrost ekspresji metylotranserazy 1 (DNMT1). Wnioski. Supresja ekspresji p53 (na poziomie mRNA i białka) będąca prawdopodobnie wynikiem zmian epigenetycznych, w szczególności hipermetylacji jego rejonu promotorowego może być związana z promocyjną aktywnością fenobarbitalu.
Źródło:
Roczniki Państwowego Zakładu Higieny; 2014, 65, 3
0035-7715
Pojawia się w:
Roczniki Państwowego Zakładu Higieny
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Polymorphisms in the p53 pathway genes and micronucleus occurrence in Chinese vinyl chloride-exposed workers
Autorzy:
Li, Yong
Feng, Nan-Nan
Zhang, Guang-Hui
Wang, Qi
Hao, Yan-Hui
Nanzhang, Ya
Long, Changxu
Li, Yongliang
Brandt-Rauf, Paul W.
Xia, Zhao-Lin
Powiązania:
https://bibliotekanauki.pl/articles/2179059.pdf
Data publikacji:
2013-12-01
Wydawca:
Instytut Medycyny Pracy im. prof. dra Jerzego Nofera w Łodzi
Tematy:
VC
occupational exposure
p53 pathway genes
genetic polymorphism
Opis:
Objectives: To investigate the association between polymorphisms in the p53 pathway genes and chromosomal damage in vinyl chloride (VC)-exposed workers. Materials and Methods: Cytokinesis block micronucleus test was performed in 310 VC-exposed workers and 149 non-exposed workers to determine chromosomal damage. The polymerase chain reaction and restriction fragment length polymorphism technique were used to detect six SNPs in the p53 pathway genes involved in the cell cycle. Results: There was a highly significant dose-response relationship between VC exposure and chromosomal damage. Individuals carrying the variant genotypes were at higher risk for chromosomal damage compared with their wild type genotype: p53rs1042522, MDM2 Del1518rs3730485, MDM2rs2279744 and GADD45Ars532446. On the other hand, individuals possessing the variant genotype of CDKN2A rs3088440 had significantly decreased risk compared with the corresponding wild-type. Conclusions: Genetic polymorphisms in P53 pathway genes may have an impact on VC-induced chromosomal damage.
Źródło:
International Journal of Occupational Medicine and Environmental Health; 2013, 26, 6; 825-836
1232-1087
1896-494X
Pojawia się w:
International Journal of Occupational Medicine and Environmental Health
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Regulation of p53 by siRNA in radiation treated cells: Simulation studies
Autorzy:
Puszyński, K.
Jaksik, R.
Świerniak, A.
Powiązania:
https://bibliotekanauki.pl/articles/331259.pdf
Data publikacji:
2012
Wydawca:
Uniwersytet Zielonogórski. Oficyna Wydawnicza
Tematy:
siRNA
p53
terapia skojarzona
combined therapy
Opis:
Ionizing radiation activates a large variety of intracellular mechanisms responsible for maintaining appropriate cell functionality or activation of apoptosis which eliminates damaged cells from the population. The mechanism of such induced cellular death is widely used in radiotherapy in order to eliminate cancer cells, although in some cases it is highly limited by increased cellular radio-resistance due to aberrations in molecular regulation mechanisms of malignant cells. Despite the positive correlation between the radiation dose and the number of apoptotic cancer cells, radiation has to be limited because of extensive side effects. Therefore, additional control signals whose role will be to maximize the cancer cells death-ratio while minimizing the radiation dose and by that the potential side effects are worth considering. In this work we present the results of simulation studies showing possibilities of single gene regulation by small interfering RNA (siRNA) that can increase radio-sensitivity of malignant cells showing aberrations in the p53 signaling pathway, responsible for DNA damage-dependant apoptosis. By blocking the production of the p53 inhibitor Mdm2, radiation treated cancer cells are pushed into the apoptotic state on a level normally achievable only with high radiation doses. The presented approach, based on a simulation study originating from experimentally validated regulatory events, concerns one of the basic problems of radiotherapy dosage limitations, which, as will be shown, can be partially avoided by using the appropriate siRNA based control mechanism.
Źródło:
International Journal of Applied Mathematics and Computer Science; 2012, 22, 4; 1011-1018
1641-876X
2083-8492
Pojawia się w:
International Journal of Applied Mathematics and Computer Science
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Wpływ ftalanu dibutylu (DBP) na poziom metylacji i ekspresji genu p53 w wątrobie szczurów Wistar
The effect of dibutyl phthalate (DBP) on the methylation and expression level of p53 gene in the liver of Wistar rats
Autorzy:
Urbanek-Olejnik, K
Liszewska, M
Kostka, G
Powiązania:
https://bibliotekanauki.pl/articles/872276.pdf
Data publikacji:
2012
Wydawca:
Narodowy Instytut Zdrowia Publicznego. Państwowy Zakład Higieny
Tematy:
ftalan dibutylu
dzialanie rakotworcze
toksycznosc
szczury
watroba
metylacja
ekspresja genow
gen p53
Opis:
Wprowadzenie. Indukowane niegenotoksycznymi kancerogenami (NGCs) zmiany metylacji DNA rozpatrywane są jako mechanizm ich toksycznego, w tym rakotwórczego działania. Cel badań. Celem podjętych badań była ocena statusu metylacji rejonu promotorowego i ekspresji genu p53 na poziomie mRNA oraz białka w wyniku oddziaływania ftalanu dibutylu (DBP). Badania zmierzały do oceny zależności pomiędzy ekspresją genu p53 a poziomem metylacji jego rejonu promotorowego. Materiał i metody. Samce szczurów szczepu Wistar otrzymywały DBP w dawce 1800 mg/kg m.c. x dzień-1 jednorazowo, 3-krotnie i 14-krotnie. Ocenę stopnia zmian metylacji badanych sekwencji CpG rejonu promotorowego genu p53 dokonano metodą MSRA (ang. Methylation-Sensitive Restriction Enzyme Analysis). Analizę względnego poziomu transkryptów badanego genu przeprowadzano metodą PCR w czasie rzeczywistym natomiast ocenę ekspresji genu na poziomie białka - techniką Western Blot. Wyniki. W wyniku oddziaływania DBP wykazano wzrost metylacji genu p53 po jednorazowym narażeniu zwierząt badanym związkiem. Nie stwierdzono bezpośredniej zależności pomiędzy poziomem ekspresji genu p53 a metylacją badanych sekwencji rejonu promotorowego genu p53. Obniżony poziom białka p53 obserwowano przez cały okres doświadczalny. Wnioski. Wykazano brak zależność pomiędzy poziomem ekspresji genu p53 a zmianami metylacji jego rejonu promotorowego. Obniżony poziom białka p53, był prawdopodobnie efektem represyjnego oddziaływania białka c-myc, uczestniczącego w tych samych szlakach transdukcji sygnału.
Background. Currently, nongenotoxic carcinogens-induced changes in DNA methylation profile are considered as mechanism of their toxicity, including carcinogenic action. Objective. The aim of the study was to determine the effect of dibutyl phthalate (DBP) on the methylation levels of the p53 promoter region, as well as mRNA and protein level of this gene. Material and method. Male Wistar rats received DBP in one, three or fourteen daily oral doses (at 24-h intervals) of 1800 mg/kg b.w. x day-1. The methylation level of c-myc gene was determined by PCR-based methylation sensitive restriction enzyme analysis (MSRA). The expression of gene was assessed by Real-Time PCR (at mRNA level) and Western blot (at protein level) analysis. Results. There was observed the hypermethylation of p53 promoter region after short (1 day) exposure of the animals to DBP. No correlation was found between mRNA expression and methylation level of p53 gene. The present study showed decreased level of p53 protein, during the whole period of study. Conclusions. No direct correlation was observed between the methylation and expression level of p53. The decreased protein level might be a consequence of the repressive effect of c-myc, which was involved in signal transduction pathways, the same as p53 protein.
Źródło:
Roczniki Państwowego Zakładu Higieny; 2012, 63, 4
0035-7715
Pojawia się w:
Roczniki Państwowego Zakładu Higieny
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation
Autorzy:
Vilasová, Zdeňka
Řezáčová, Martina
Vávrová, Jiřina
Tichý, Aleš
Vokurková, Doris
Zoelzer, Friedo
Řeháková, Zuzana
Osterreicher, Jan
Lukášová, Emilie
Powiązania:
https://bibliotekanauki.pl/articles/1040760.pdf
Data publikacji:
2008
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
lymphocyte
ionizing radiation
p53
phytohemagglutinin (PHA)
apoptosis
DNA damage
Opis:
The main aim of this study was to compare the reaction of quiescent and proliferating, i.e. phytohemagglutinin (PHA)-stimulated, human peripheral blood mononuclear cells (PBMCs) to γ-radiation, and analyse changes of proteins related to repair of DNA damage and apoptosis, such as γH2A.X, p53, p53 phosphorylation at serines-15 and -392, and p21 and their dose dependence. Freshly isolated PBMCs in peripheral blood are predominantly quiescent, in G0 phase, and with very low amounts of proteins p53 and p21. Using confocal microscopy we detected dose dependent (0.5-5 Gy) induction of foci containing γH2A.X (1 h after γ-ray exposure), which are formed around radiation-induced double strand breaks of DNA. Apoptosis was detected from 24 h after irradiation by the dose of 4 Gy onwards by Annexin V binding and lamin B cleavage. Seventy two hours after irradiation 70% of CD3+ lymphocytes were A+. Neither increase in p53 nor its phosphorylation on serine-392 after irradiation was detected in these cells. However, massive increase in p21 (cyclin-dependent kinase inhibitor 1A) was detected after irradiation, which can be responsible for late occurrence of apoptosis in these quiescent cells. PHA-stimulation itself (72 h) caused an increase in early apoptosis (A+PI-) in comparison to non-stimulated PBMCs (38% A+ resp. 13.4%). After PHA-stimulation also the amount of γH2A.X, p53, and p21 increased, but no phosphorylation of p53 on serine-392 or -15 was detected. Reaction to γ-radiation was different in PHA-stimulated lymphocytes: the p53 pathway was activated and p53 was phosphorylated on serines-15 and -392 4 h after irradiation by the dose of 4 Gy. Phosphorylation of p53 at serine-15 increased in a dose-dependent manner in the studied dose range 0.2-7.5 Gy. Also the amount of p21 increased after irradiation. Seventy two hours after irradiation of PHA-stimulated CD3+ T lymphocytes by the dose of 4 Gy 65% of cells were A+.
Źródło:
Acta Biochimica Polonica; 2008, 55, 2; 381-390
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
Indukowana fenobarbitalem hipermetylacja rejonu promotorowego genu p53 w watrobie szczurow szczepu Wistar
Phenobarbital-induced hypermethylation of the p53 promoter region in the liver of Wistar rats
Autorzy:
Kostka, G
Urbanek-Olejnik, K.
Wiadrowska, B.
Bankowski, R.
Powiązania:
https://bibliotekanauki.pl/articles/876498.pdf
Data publikacji:
2008
Wydawca:
Narodowy Instytut Zdrowia Publicznego. Państwowy Zakład Higieny
Tematy:
zwierzeta doswiadczalne
szczury
watroba
gen p53
hipermetylacja
fenobarbital
synteza DNA
metylotransferaza DNA
metylacja DNA
experimental animal
rat
liver
p53 gene
hypermethylation
phenobarbital
DNA synthesis
DNA methyltransferase
DNA methylation
Opis:
Indukowane niegenotoksycznymi kancerogenami (NGCs) zmiany metylacji DNA rozpatrywane są jako mechanizm ich toksycznego, w tym rakotwórczego działania. Zbadano wpływ fenobarbitalu (PB), na poziom metylacji regionu promotorowego genu p53 w wątrobie szczurów szczepu Wis tar. Zmiany metylacji genu p53 korelowano z syntezą DNA, aktywnością metylotransferaz DNA (DNMTs) oraz z masą wątroby. Samce szczurów szczepu Wistar otrzymywały PB w dawce wynoszącej 98,2 mg/ kg m.c. x dzień-1 jednorazowo, 3-krotnie i 14-krotnie. Wykazano, że PB wywoływał hipermetylację w badanych sekwencjach rejonu promotorowego genu p53. Indukowana PB hipermetylacja genu występowała w przebiegu całego okresu doświadczalnego. Stymulację syntezy DNA, która poprzedzała wzrost masy wątroby oraz indukcję DNMTs, wykazano tylko po 1 i 3 dawkach związku. Kontynuowanie narażenia zwierząt na PB (14 dawek) nie wywoływało zmian w syntezie DNA i aktywności DNMTs w porównaniu do kontroli. Przypuszcza się, że indukowana PB de novo metylacja rejonu promotorowego genu p53, nie była związana z aktywnością DNMTs.
Non-genotoxic carcinogens (NGCs)-induced changes of DNA methylation has been proposed as a mechanism of their toxicity, including carcinogenic action. The effect of phénobarbital (PB), a rodent liver carcinogen on the methylation level of the p53 promoter region in rat liver was studied. Changes in the methylation status of the p53 gene were correlated with changes in DNA synthesis, DNA methyltransferase (DNMTs) activity and liver weight. Male Wistar rats received PB in one, three or fourteen daily oral doses of 92.8 mg/kg b.w. x day-1. We have demonstrated that PB increased the methylation of the p53 gene. Cytosine hypermethylation in the analyzed CpG sites of the p53 gene promoter occurred during the whole period of study. However, an increase in DNA synthesis was only observed after 1 and 3 days of treatment with PB and it preceded liver growth. Treatment of rats with PB for 1 and 3 days also produced an increase in nuclear DNMTs activity. After prolonged administration (14 days), no changes in DNMTs activity nor DNA synthesis were observed. It is proposed that PB- induced de novo methylation of the p53 gene was not associated with DNMTs activity.
Źródło:
Roczniki Państwowego Zakładu Higieny; 2008, 59, 4; 455-465
0035-7715
Pojawia się w:
Roczniki Państwowego Zakładu Higieny
Dostawca treści:
Biblioteka Nauki
Artykuł
Tytuł:
p53-dependent suppression of the human calcyclin gene (S100A6): the role of Sp1 and of NFκB
Autorzy:
Króliczak, Weronika
Pietrzak, Maciej
Puzianowska-Kuznicka, Monika
Powiązania:
https://bibliotekanauki.pl/articles/1040715.pdf
Data publikacji:
2008
Wydawca:
Polskie Towarzystwo Biochemiczne
Tematy:
gene suppression
wild type and mutant p53
Sp1
calcyclin gene (S100A6)
NFκB
Opis:
Calcyclin (S100A6) is believed to participate in cell cycle control. It was, however, unclear if its expression depends on p53, a key regulator of apoptosis and cell cycle. We therefore performed transcription regulation assays in HeLa cells and found that wild type p53 suppressed the S100A6 promoter up to 12-fold in a dose-dependent manner. In contrast, the well-characterized V143A, R175H, R249S, and L344A p53 mutants cloned from human cancers suppressed this promoter with a 6 to 9-fold lower efficiency. All the sites mediating the p53-dependent suppression were contained in the -167 to +134 fragment of the S100A6 promoter. Separate overexpression of either Sp1 or of NFκB only partially counteracted the p53 inhibitory effect on the S100A6 promoter, while simultaneous overexpression of both these transactivators resulted in a complete abolishment of the p53 inhibitory effect on this promoter. Sp1 and NFκB binding to the probes resembling their putative binding sites present in the S100A6 promoter was decreased in the presence of wild type p53. We propose that the suppression of S100A6 is yet another mechanism by which p53 inhibits proliferation. Insufficient suppression of this gene by p53 mutants could well be responsible for calcyclin overexpression and cell cycle deregulation observed in cancer tissues.
Źródło:
Acta Biochimica Polonica; 2008, 55, 3; 559-570
0001-527X
Pojawia się w:
Acta Biochimica Polonica
Dostawca treści:
Biblioteka Nauki
Artykuł

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