Wyniki wyszukiwania - Biblioteka Nauki

1

p53 protein expression in oral squamous cell cancer in relation to some its clinicopathological variables

100%

Sulkowska M. , Famulski W. , Miller-Famulska D. , Terlikowski S. , Kasacka I. , Gnojnicki I.

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tom 39

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nr 1

2

Analysis of p-53 protein expression in diffuse and intestinal types of gastric carcinoma

100%

Chibowska I. , Chibowski D. , Skomra D. , Szumilo J.

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tom 39

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nr 1

3

PCNA and p53 expression in relation to clinicopathological features of oral papilloma

88%

Sulkowski S. , Famulski W. , Kasacka J. , Sulkowska M. , Klimiuk A.

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tom 39

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nr 1

4

TNFalpha-induced activation of NFkappaB protects against UV-induced apoptosis specifically in p53-proficient cells

75%

Szoltysek K. , Pietranek K. , Kalinowska-Herok M. , Pietrowska M. , Kimmel M. , Widlak P.

Acta Biochimica Polonica

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2008

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tom 55

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nr 4

741-748

EN

The signaling pathways that depend on p53 or NFκB transcription factors are essential components of cellular responses to stress. In general, p53 is involved in either activation of cell cycle arrest or induction of apoptosis, while NFκB exerts mostly anti-apoptotic functions; both regulatory pathways apparently interfere with each other. Here we aimed to analyze the effects of NFκB activation on DNA damage-induced apoptosis, either p53-dependent or p53-independent, in a set of human cell lines. Four cell lines, HCT116 and RKO colon carcinoma, NCI-H1299 lung carcinoma and HL60 myeloblastoma, each of them in two congenic variants either containing or lacking transcriptionally competent p53, were used. Cells were incubated with TNFα cytokine to activate NFκB and then treated with ultraviolet or ionizing radiation to induce apoptosis, which was assessed by measurement of the sub-G1 cell fraction. We observed that treatment with TNFα resulted in a significant reduction in the frequency of apoptotic cells in UV-irradiated p53-proficient lines (with exception of the UV-resistant NCI-H1299 cells). This anti-apoptotic effect was lost when cells were pretreated with parthenolide, an inhibitor of NFκB activation. In marked contrast, TNFα-pretreatment of p53-deficient lines resulted in an increased frequency of apoptotic cells after UV irradiation (with exception of HL60 cells). Such anti- and pro-apoptotic influence of TNFα was less obvious in cells treated with ionizing radiation. The data clearly indicates functional interference of both signaling pathways upon the damage-induced apoptotic response, yet the observed effects are both cell type- and stimulus-specific.

5

Effect of aging and oxidative/genotoxic stress on poly(ADP-ribose) polymerase-1 activity in rat brain

75%

Strosznajder R. P. , Jesko H. , Adamczyk A.

Acta Biochimica Polonica

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2005

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tom 52

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nr 4

909-914

EN

Poly(ADP-ribose) polymerase-1 (PARP-1, EC 2.4.2.30), a DNA-bound enzyme, plays a key role in genome stability, but after overactivation can also be responsible for cell death. The aim of the present study was to investigate PARP-1 activity in the hippocampus, brain cortex, striatum and cerebellum in adult (4 months) and aged (24 months) specific pathogen free Wistar rats and to correlate it with PARP-1 protein level and p53 expression. Moreover, the response of PARP-1 in adult and aged hippocampus to oxidative/genotoxic stress was evaluated. Our data indicated a statistically significant enhancement of PARP-1 activity in aged hippocampus and cerebral cortex comparing to adults without statistically significant changes in PARP-1 protein level. The expression of p53 mRNA was elevated in all aged brain parts with the exception of the cerebral cortex. Our data suggest that enhancement of PARP-1 activity and p53 expression in aged brain may indicate higher DNA damage. Our data also indicate that during excessive oxidative/genotoxic stress there is no response of PARP-1 activity in aged hippocampus in contrast to a significant enhancement of PARP-1 activity in adults which may have important consequences for the physiology and pathology of the brain.

6

Chemotherapy increases p53 protein phosphorylated at serine 392 in recurrent primary squamous cell lung cancer

75%

Holownia A. , Mroz R. M. , Kozlowski M. , Chyczewska E. , Laudanski J. , Chyczewski L. , Braszko J. J.

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tom 39

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nr 1

7

Role of poly[ADP-ribose] polymerase in the regulation of the stability of wild-type p53 protein and p53-mediated apoptosis

75%

Wesierska-Gadek J.

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2000

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tom 05

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nr 2

8

Advantage of a baculovirus expression system for protein-protein interaction studies. Involvement of posttranslational phosphorylation in the interaction between wt p53 protein and poly[ADP-ribose] polymerase-1

75%

Schmid G. , Wojciechowski J. , Wesierska-Gadek J.

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nr 3

EN

We recently observed an interaction between poly(ADP-ribose) polymerase-1 (PARP-1) and the tumor suppressor p53 protein. However, more extensive studies on both proteins, especially those on characterization of their domains involved in the interaction were difficult due to very low expression levels of p53 in mammalian cells. Therefore, we generated recombinant proteins for such studies. To clarify which domains of human PARP-1 and of human wild-type (wt) p53 were involved in this protein-protein interaction, we generated baculoviral constructs encoding full length or distinct functional domains of both proteins. Full length PARP-1 was simultaneously coexpressed in insect cells with full length wt p53 protein or its distinct truncated fragments and vice versa. Reciprocal immunoprecipitation of Sf9 cell lysates revealed that the central and carboxy-terminal fragments of p53 each were sufficient to confer binding to PARP-1, whereas the amino-terminal part harbouring the transactivation functional domain was dispensable. On the other hand, the amino-terminal and central fragments of PARP-1 were both necessary for complex formation with p53 protein. Since the most important features of p53 protein are regulated by phosphorylation, we addressed the question whether its phosphorylation is essential for the binding between the two proteins. Baculovirally expressed wt p53 was post-translationally modified. At least six distinct p53 isomers were resolved by immunoblotting following two-dimensional separation of baculovirally expressed wt p53 protein. Using specific phospho-serine antibodies, we identified phosphorylation of baculovirally expressed p53 protein at five distinct sites. To define the role of p53 phosphorylation, pull-down assays using untreated and dephosphorylated p53 protein were performed. Dephosphorylated p53 failed to bind PARP-1, indicating that complex formation between the two proteins was regulated by phosphorylation of p53. The marked phosphorylation of p53 at Ser392 observed in unstressed cells suggests that the phosphorylated carboxy-terminal part of p53 undergoes complex formation with PARP-1 resulting in masking of the NES and thereby preventing its export.

9

The subcellular distribution of the p53 tumour suppressor, and organismal ageing

75%

Wesierska-Gadek J. , Schmid G.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr 3

10

p53, MDM 2, bcl-2 staining in follicular neoplasms of the thyroid gland

75%

Czyz W. , Pasieka Z. , Kuzdak K. , Timler D. , Brzezinski J.

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tom 39

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nr 1

11

p53 protein expression in gastric cancer cells - its correlation with clinicopathological features and selected serum neoplasmatic markers

63%

Furtak J. , Zinkiewicz K. , Zgodzinski W. , Szumilo J. , Borzecki A. , Wallner G. , Baranowski W.

Polish Journal of Environmental Studies

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2004

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tom 13

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nr Suppl.2, Part 1

EN

The aim of the present study was to assess the possible correlation of p53 with CEA and Ca 19-9 serum levels as well as with selected clinicopathological data. 46 patients, who were gastrectomized due to gastric cancer between 1998 and 2001, were analyzed. The concentration of CEA and Ca 19.9 was estimated in serum. Mean percentage of p53-positive cells in present group was 33,69 %. The comparison of mean percentage of p53-positive cells with IHC reaction intensity revealed statistically significant, directly proportional correlation, with p<0,001. Mean CEA and Ca 19-9 serum concentration were 1,75± 1,71 ng/ml, and 17,34±44,73 U/ml respectively. No significant correlation between p53-expression, CEA and Cal9-9 was noted respecting several clinicopathological data of tumors. However clear trend of higher CEA and Cal9-9 values in groups of potentially worse prognosis (T3-T4; Nl-2; III grade of disease) was observed.

12

Prognostic status of p53 protein accumulation in canine malignant mammary tumours

63%

Lopuszynski W. , Szczubial M. , Komsta R.

Bulletin of the Veterinary Institute in Puławy

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2010

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tom 54

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nr 1

105-111

EN

The expression of p53 protein was determined by the immunohistochemical study with CM-1 polyclonal antibody. The investigations were performed on formalin-fixed and paraffin-embedded tissue samples of mammary tumours obtained from 131 bitches during surgery. The p53 protein accumulation was detected in 37 tumours (28.24%). No correlation was found between p53 protein overexpression and histological type, tumour size, or regional lymph node status. However, its relationship with a histologic malignant grade approached statistical significance (P=0.067). After the 24-month follow-up period, survival analysis revealed a shortened disease-free survival and overall survival time of the dogs with tumours, which overexpressed p53 protein. Only in the case of survival time, the difference was close to the borderline of statistical significance (P=0.061). The research data presented herein, being not fully explicit, have indicated a correlation of p53 protein accumulation with worse prognosis in canine mammary tumours, although the results do not allow recognising p53 protein accumulation as a suitable prognostic factor.

13

Switching p53-dependent growth arrest to apoptosis via the inhibition of DNA damage-activated kinases

63%

Hublarova P. , Greplova K. , Holcakova J. , Vojtesek B. , Hrstka R.

Cellular and Molecular Biology Letters

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2010

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tom 15

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nr 3

473-484

EN

Cisplatin and doxorubicin are widely used anticancer drugs that cause DNA damage, which activates the ATM-Chk2-p53 pathway in cancer cells. This activation leads to cell cycle block or apoptosis, depending on the nature of the DNA damage. In an attempt to enhance the effects of these agents, we inhibited ATM/ATR and Chk2, which are known upstream regulators of p53. The cancer cell lines A2780 and ARN8, bearing the wild-type p53 protein, were used to study changes in p53 activation and trans-activation. Our results suggest that the G1-checkpoint, normally activated by DNA damage, is functionally overcome by the action of kinase inhibitors that sensitize cells to apoptosis. Both inhibitors show these effects, albeit with variable intensity in different cell lines, which is promising for other studies and theoretically for use in clinical practice.

14

Immunohistochemical localization of metallothionein and p53 protein in pancreatic serous cystadenomas

63%

Sliwinska-Mosson M. , Milnerowicz H. , Rabczynski J. , Milnerowicz S.

Archivum Immunologiae et Therapiae Experimentalis

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2009

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tom 57

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nr 4

295-301

15

Decreased secretion of vascular endothelial growth factor is associated with increased apoptosis in vascular tumor derived endothelial cells

63%

Mebeta P.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 4

16

Effects of p53 inhibitor on survival and death of cells subjected to oxidative stress

63%

Strosznajder R. P. , Jesko H. , Banasik M. , Tanaka S.

Journal of Physiology and Pharmacology. Supplement

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2005

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tom 56

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nr 4

215-221

EN

Our previous data indicate that ischemia and amyloid beta peptide (Abeta) cause an oxidative damage to macromolecules. In the present study we investigated the role of p53 protein in cell survival and death after administration of Abeta. The experiments were carried out on pheochromocytoma cells (PC-12) and cortical primary neurons in culture. The cortical neurons were exposed (48 h, 10 µM) to the action of a short Abeta25-35 neurotoxic fragment and the involvement of p53 was evaluated after addition of the p53 inhibitor pifithrin-alpha. Changes in cell morphology were evaluated by 4', 6-diamidino-2-phenylindole staining and the concentration-dependent effect of pifithrin-alpha on cells viability was determined. Additionally, we studied the effect of pifithrin-alpha on neuronal survival in vivo after a 5-min global brain ischemia followed by 7 days' reperfusion in gerbils. We found that Abeta enhanced apoptotic cell death in cortical primary neurons. Pifithrin-alpha, at a 10 µM final concentration, protected the neuronal cells from the apoptotic death. However, at concentrations of 0.1 and 1 mM, the p53 inhibitor decreased PC-12 cells' viability in a dose-dependent manner. In in vivo experiments we did not observe any neuroprotection by pifithrin-alpha in the CA1 hippocampal layer, which suggests that its effects strongly depend on the duration and type of an ischemic insult. Our data indicate that pifithrin-alpha affects neuronal cells in a dual manner. It has a protective effect at a low concentration, but becomes neurotoxic at higher concentrations.

17

Prognostic significance of p53 protein accumulation in cancer cells obtained from selected group of patients with sporadic colorectal cancer

63%

Paluszkiewicz P. , Karski J. , Berbec H. , Pawlowska-Wakowicz B. , Cybulski M. , Karski M. , Paszkowska A.

Journal of Applied Genetics

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1999

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tom 40

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nr 2

18

Poly[ADP-ribose] polymerase-1 regulates the stability of the wild-type p53 protein

63%

Wesierska-Gadek J. , Schmid G.

Cellular and Molecular Biology Letters

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2001

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tom 06

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nr 2

19

Quantification of P21 mRNA in biopsy specimens of colon tissue at different stages of neoplastic transformation

63%

Dzierzewicz Z. , Kwapisz I. , Orchel A. , Hudyka K. , Wilczok T.

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tom 39

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nr 1

20

Sodium nitroprusside, a nitric oxide donor, fails to bypass the block of neuronal differentiation in PC12 cells imposed by a dominant negative Ras protein

51%

Bator J. , Varga J. , Berta G. , Barbakadze T. , Mikeladze D. , Ramsden J. , Szeberenyi J.

Cellular and Molecular Biology Letters

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2012

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tom 17

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nr 3

EN

Nitric oxide (NO) is a mediator of a diverse array of inter- and intracellular signal transduction processes. The aim of the present study was to analyze its possible role as a second messenger in the process of neuronal differentiation of PC12 pheochromocytoma cells. Upon NGF treatment wildtype PC12 cells stop dividing and develop neurites. In contrast, a PC12 subclone (designated M-M17-26) expressing a dominant-negative mutant Ras protein keeps proliferating and fails to grow neurites after NGF treatment. Sodium nitroprusside (SNP), an NO donor, was found to induce the p53 protein and to inhibit proliferation of both PC12 and M-M17-26 cells, but failed to induce neuronal differentiation in these cell lines. Key signaling pathways (the ERK and Akt pathways) were also not affected by SNP treatment, and the phosphorylation of CREB transcription factor was only slightly stimulated. It is thus concluded from the results presented in this paper that NO is unable to activate signaling proteins acting downstream or independent of Ras that are required for neuronal differentiation.