Search results

1

Association of EGF and p53 gene polymorphisms and colorectal cancer risk in the Slovak population

100%

Mahmood S., Sivoňová M., Matáková T., Dobrota D., Wsólová L., Dzian A., Mištuna D.

Open Medicine

|

2014

|

vol. 9

|

issue 3

405-416

EN

During the transformation process single nucleotide polymorphisms (SNPs) of key genes, such as p53 Arg72Pro or EGF A61G, may mediate various cellular processes. These variants may be associated with colorectal cancer risk (CRC), but conflicting findings have been reported. The purpose of this study was to determine the association of the SNPs in 5′ UTR of EGF A61G and p53 Arg72Pro and CRC in the Slovak population. The present case-control study was carried out in 173 confirmed CRC patients and 303 healthy subjects. Genotyping was performed by PCR-RFLP methods. Significant association was observed between age and CRC risk (p=0.001). Lower CRC risk was seen in younger patients carrying genotype p53 Arg72Pro (0.14; 95% CI 0.02–0.99, p=0.049). Gender-stratified analysis showed a significant inverse association of the polymorphism EGF G61G with CRC risk (0.48; 95% CI 0.2–0.9, p=0.04) only in male patients. Tumour site genotype distribution revealed that female patients with localized colon cancer were significantly associated with p53 Pro72Pro genotype (4.0; 95% CI 1.27–12.7, p=0.04) whereas the cancer of rectosigmoid junction was associated with the EGF G61G genotype (4.5; 95% CI 1.2–16.97, p=0.02). Combination of p53 Arg72Pro or EGF A61G polymorphisms were not associated with CRC risk by using logistic regression.

2

Evaluation of Selected Indicators of Apoptosis in Patients with Thyroid Tumors

100%

Kołomecki K., Maciaszczyk P., Stępień H., Cywiński J., Cielecka J., Stępień T., Kuzdak K.

Polish Journal of Surgery

|

2007

|

vol. 79

|

issue 2

85-91

EN

The aim of the study. Estimatation of p53 protein and soluble FasL ligand level concentration in serum of patients with benign and malignant primary follicular thyroid tumors as indicators of apoptosis and evaluation of their usefulness for early diagnosis of thyroid tumors.Material and methods. 42 patients were qualified for the study. 28 patients were diagnosed with follicular neoplasm (NF) in preoperative fine-needle biopsy. The final verification was postoperative histopathology. Control group consisted of 14 patients with euthyroid goiter, with no cancerous cells detected in cytologic examination. All patients underwent surgical procedures. Levels of p53 and sFasL were marked on the day of admission, before surgery. Destinationes were made in the serum using the ELISA immunoenzymatic method. Obtained data underwent computer statistical analysis.Results. The analysis revealed significantly higher sFasL and p53 concentration in blood of patients with follicular thyroid cancer in comparison with the control group. Similarly, p53 serum level was significantly higher in case of patients with benign thyroid adenoma than in the control group. Comparison between p53 and sFasL serum level in cases of patients with follicular cancer and follicular adenoma showed statistically higher sFasL blood concentration in cases of patients with follicular cancer; there was no statistically significant connection in case of p53 concentration.Conclusions. 1. sFasL and p53 serum concentration are significantly higher in patients with follicular thyroid cancer than in the control group. 2.The p53 serum concentration is significantly higher in cases of all patients with benign thyroid adenoma than in the control group. There was no such correlation for sFasL concentration. 3. sFasL serum concentration is significantly higher in cases of patients with follicular thyroid cancer than in patients with benign thyroid adenoma. There was no such correlation with serum levels of p53.

3

Quantitative analysis of the level of p53 and p21WAF1 mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate

88%

Węglarz L., Molin I., Orchel A., Parfiniewicz B., Dzierżewicz Z.

Acta Biochimica Polonica

|

2006

|

vol. 53

|

issue 2

349-356

EN

The aim of this study was to analyze the molecular mechanism of inositol hexaphosphate (InsP6) action through which it may inhibit proliferation of colon cancer cells and cell cycle progression. A kinetic study of p53 and p21WAF1 mRNA increase was performed on human colon cancer HT-29 cells after treatment with 1, 5 and 10 mM InsP6 for 6, 12, 24 and 48 h. Real-time-QPCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The transcription of β-actin and GAPDH genes was assessed in parallel to select the control gene with least variability. The 2-ΔΔCt method was used to analyze the relative changes in gene transcription. InsP6 stimulated p53 and p21WAF1 expression at the mRNA level, with the highest increase in p21WAF1 mRNA occurring at 24 h, i.e., following the highest increase in p53 mRNA observed at 12 h. Based on these studies it may be concluded that the ability of InsP6 to arrest the cell cycle may be mediated by the transcriptional up-regulation of the p53-responsive p21WAF1 gene.

4

GENTIAN VIOLET: WHAT WE KNOW AND WHAT IS AHEAD OF US

88%

Dragan J., Michalak S. S.

Acta Poloniae Pharmaceutica - Drug Research

|

2019

|

vol. 76

|

issue 3

389-396

EN

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.

5

Influence of G arrest on the cytotoxicity of DNA topoisomerase inhibitors toward human carcinoma cells with different p53 status.

88%

Bozko P., Larsen A. K., Raymond E., Skladanowski A.

|

vol. 49

|

issue 1

109-119

EN

We here report the influence of the cell cycle abrogator UCN-01 on RKO human colon carcinoma cells differing in p53 status following exposure to two DNA damaging agents, the topoisomerase inhibitors etoposide and camptothecin. Cells were treated with the two drugs at the IC90 concentration for 24 h followed by post-incubation in drug-free medium. RKO cells expressing wild-type, functional p53 arrested the cell cycle progression in both the G1 and G2 phases of the cell cycle whereas the RKO/E6 cells, which lack functional p53, only arrested in the G2 phase. Growth-arrested cells did not resume proliferation even after prolonged incubation in drug-free medium (up to 96 h). To evaluate the importance of the cell cycle arrest on cellular survival, a non-toxic dose of UCN-01 (100 nM) was added to the growth-arrested cells. The addition of UCN-01 was accompanied by mitotic entry as revealed by the appearance of condensed chromatin and the MPM-2 phosphoepitope, which is characteristic for mitotic cells. G2 exit and mitotic transit was accompanied by a rapid activation of caspase-3 and apoptotic cell death. The influence of UCN-01 on the long-term cytotoxic effects of the two drugs was also determined. Unexpectedly, abrogation of the G2 arrest had no influence on the overall cytotoxicity of either drug. In contrast, addition of UCN-01 to cisplatin-treated RKO and RKO/E6 cells greatly increased the cytotoxic effects of the alkylating agent. These results strongly suggest that even prolonged cell cycle arrest in the G2 phase of the cell cycle is not necessarily coupled to efficient DNA repair and enhanced cellular survival as generally believed.

6

Gamma-radiation-induced ATM-dependent signalling in human T-lymphocyte leukemic cells, MOLT-4

88%

Tichý A., Záškodová D., Řezáčová M., Vávrová J., Vokurková D., Pejchal J., Vilasová Z., Cerman J., Österreicher J.

Acta Biochimica Polonica

|

2007

|

vol. 54

|

issue 2

281-287

EN

ATM kinase (ATM) is essential for activation of cell cycle check points and DNA repair in response to ionizing radiation (IR). In this work we studied the molecular mechanisms regulating DNA repair and cell death in human T-lymphocyte leukemic cells, MOLT-4. Apoptosis was evaluated by flow-cytometric detection of annexin V. Early apoptotic cells were determined as sub-G1 cells and late apoptotic cells were determined as APO2.7-positive ones. Proteins involved in ATM signalling pathway were analysed by Western-blotting. We observed a rapid (0.5 h) phosphorylation of ATM declining after 6 h after irradiation by all the doses studied (1.5, 3.0, and 7.5 Gy). Checkpoint kinase-2 (Chk-2) was also phosphorylated after 0.5 h but its phosphorylated form persisted 4, 2, and 1 h after the doses of 1.5, 3.0, and 7.5 Gy, respectively. The amount of p53 protein and its form phosphorylated on Ser-392 increased 1 h after irradiation (1-10 Gy). The lethal dose of 7.5 Gy caused an immediate induction and phosphorylation of p53 after 0.5 h post-irradiation. At the time of phosphorylation of p53, we found simultaneous phosphorylation of the oncoprotein Mdm2 on Ser-166. Neither ATM nor its downstream targets showed a dose-dependent response after 1 h when irradiated by the doses of 1-10 Gy. MOLT-4 cells were very sensitive to the effect of IR. Even low doses, such as 1.5 Gy, induced apoptosis 16 h after irradiation (evaluated according to the cleavage of nuclear lamin B to a 48-kDa fragment). IR-induced molecular signalling after exposure to all the tested doses was triggered by rapid phosphorylation of ATM and Chk-2. Subsequent induction of p53 protein and its phosphorylation was accompanied by concomitant phosphorylation of its negative regulator, oncoprotein Mdm2, and followed by induction of apoptosis.

7

Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation

75%

Vilasová Z., Řezáčová M., Vávrová J., Tichý A., Vokurková D., Zoelzer F., Řeháková Z., Osterreicher J., Lukášová E.

Acta Biochimica Polonica

|

2008

|

vol. 55

|

issue 2

381-390

EN

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+.

8

The role of E2F2 in signaling pathways associated with cancer pathogenesis and potential treatment: A review of current studies

75%

Domańska J., Poboży K., Domański P., Fudalej M., Deptała A., Badowska-Kozakiewicz A.

OncoReview

|

2023

|

vol. 13

|

issue 2

58-66

EN

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.

9

Prospects for p53-based cancer therapy.

75%

Stokłsa T., Gołąb J.

Acta Biochimica Polonica

|

2005

|

vol. 52

|

issue 2

321-328

EN

The p53 tumor suppressor plays the role of a cellular hub which gathers stress signals such as damage to DNA or hypoxia and translates them into a complex response. p53 exerts its action mainly as a potent transcription factor. The two major outcomes of p53 activity are highlighted: cell cycle arrest and apoptosis. During malignant transformation p53 or p53-pathway related molecules are disabled extremely often. Mutations in p53 gene are present in every second human tumor. A mutant form of p53 may not only negate the wild type p53 function but may play additional role in tumor progression. Therefore p53 represents a relatively unique and specific target for anticancer drug design. Current approaches include several different molecules able to restore p53 wild-type conformation and activity. Such small molecule drugs hold great promise in treating human tumors with dysfunction of p53 pathway in the near future.

10

The role of the 5' terminal region of p53 mRNA in the p53 gene expression

75%

Swiatkowska A., Zydowicz P., Sroka J., Ciesiołka J.

Acta Biochimica Polonica

|

2016

|

vol. 63

|

issue 4

645-651

EN

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.

11

Apoptotic factors in physiological and pathological processes of teeth and periodontal tissues – literature review

75%

Orzedala-Koszel U., Rahnama M., Lobacz M., Koszel H.

|

vol. 27

|

issue 4

229-233

EN

Apoptosis is a physiological process that occurs in the human body throughout the entire life span. This process can be seen in the tissues of the stomatognathic system. A disorder in such programmed cell death processes leads to the development of pathological lesions. Among these are inflammation, osteolytic lesions and neoplastic hyperplasia. We put forward that future studies should concentrate on how to use the knowledge of apoptotic processes and their inhibitors in therapeutic processes involving the stomatognathic system.

12

Sequence-specific p53 gene damage by chloroacetaldehyde and its repair kinetics in Escherichia coli

63%

Kowalczyk P., Cieśla J. M., Saparbaev M., Laval J., Tudek B.

Acta Biochimica Polonica

|

2006

|

vol. 53

|

issue 2

337-347

EN

Oxidative stress and certain environmental carcinogens, e.g. vinyl chloride and its metabolite chloroacetaldehyde (CAA), introduce promutagenic exocyclic adducts into DNA, among them 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC) and N2,3-ethenoguanine (εG). We studied sequence-specific interaction of the vinyl-chloride metabolite CAA with human p53 gene exons 5-8, using DNA Polymerase Fingerprint Analysis (DPFA), and identified sites of the highest sensitivity. CAA-induced DNA damage was more extensive in p53 regions which revealed secondary structure perturbations, and were localized in regions of mutation hot-spots. These perturbations inhibited DNA synthesis on undamaged template. We also studied the repair kinetics of CAA-induced DNA lesions in E. coli at nucleotide resolution level. A plasmid bearing full length cDNA of human p53 gene was modified in vitro with 360 mM CAA and transformed into E. coli DH5α strain, in which the adaptive response system had been induced by MMS treatment before the cells were made competent. Following transformation, plasmids were re-isolated from transformed cultures 35, 40, 50 min and 1-24 h after transformation, and further subjected to LM-PCR, using ANPG, MUG and Fpg glycosylases to identify the sites of DNA damage. In adaptive response-induced E. coli cells the majority of DNA lesions recognized by ANPG glycosylase were removed from plasmid DNA within 35 min, while MUG glycosylase excised base modifications only within 50 min, both in a sequence-dependent manner. In non-adapted cells resolution of plasmid topological forms was perturbed, suggesting inhibition of one or more bacterial topoisomerases by unrepaired ε-adducts. We also observed delayed consequences of DNA modification with CAA, manifesting as secondary DNA breaks, which appeared 3 h after transformation of damaged DNA into E. coli, and were repaired after 24 h.

Refine search results

Association of EGF and p53 gene polymorphisms and colorectal cancer risk in the Slovak population

Evaluation of Selected Indicators of Apoptosis in Patients with Thyroid Tumors

Quantitative analysis of the level of p53 and p21WAF1 mRNA in human colon cancer HT-29 cells treated with inositol hexaphosphate

GENTIAN VIOLET: WHAT WE KNOW AND WHAT IS AHEAD OF US

Influence of G arrest on the cytotoxicity of DNA topoisomerase inhibitors toward human carcinoma cells with different p53 status.

Gamma-radiation-induced ATM-dependent signalling in human T-lymphocyte leukemic cells, MOLT-4

Changes in phosphorylation of histone H2A.X and p53 in response of peripheral blood lymphocytes to gamma irradiation

The role of E2F2 in signaling pathways associated with cancer pathogenesis and potential treatment: A review of current studies

Prospects for p53-based cancer therapy.

The role of the 5' terminal region of p53 mRNA in the p53 gene expression

Apoptotic factors in physiological and pathological processes of teeth and periodontal tissues – literature review

Sequence-specific p53 gene damage by chloroacetaldehyde and its repair kinetics in Escherichia coli