Browsing by Subject "p53"

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  • Lantto, Tiina A.; Laakso, Into; Dorman, H. J. Damien; Mauriala, Timo; Hiltunen, Raimo; Köks, Sulev; Raasmaja, Atso (2016)
    Plant phenolics have shown to activate apoptotic cell death in different tumourigenic cell lines. In this study, we evaluated the effects of juniper berry extract (Juniperus communis L.) on p53 protein, gene expression and DNA fragmentation in human neuroblastoma SH-SY5Y cells. In addition, we analyzed the phenolic composition of the extract. We found that juniper berry extract activated cellular relocalization of p53 and DNA fragmentation-dependent cell death. Differentially expressed genes between treated and non-treated cells were evaluated with the cDNA-RDA (representational difference analysis) method at the early time point of apoptotic process when p53 started to be activated and no caspase activity was detected. Twenty one overexpressed genes related to cellular stress, protein synthesis, cell survival and death were detected. Interestingly, they included endoplasmic reticulum (ER) stress inducer and sensor HSPA5 and other ER stress-related genes CALM2 and YKT6 indicating that ER stress response was involved in juniper berry extract mediated cell death. In composition analysis, we identified and quantified low concentrations of fifteen phenolic compounds. The main groups of them were flavones, flavonols, phenolic acids, flavanol and biflavonoid including glycosides of quercetin, apigenin, isoscutellarein and hypolaetin. It is suggested that juniper berry extract induced the p53-associated apoptosis through the potentiation and synergism by several phenolic compounds.
  • Huvila, Jutta; Laajala, Teemu D.; Edqvist, Per-Henrik; Mardinoglu, Adil; Talve, Lauri; Ponten, Fredrik; Grenman, Seija; Carpen, Olli; Aittokallio, Tero; Auranen, Annika (2018)
    Objective. In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods. A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results. A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (295%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P <0.001) of dying of EEC compared to the low-risk group. Conclusions. P53 and ASRGL1 immunoprofiling stratifies EEC patients into three risk groups with significantly different outcomes. This simple and easily applicable panel could provide a useful tool in EEC risk stratification and guiding the allocation of treatment modalities. (C) 2018 Elsevier Inc. All rights reserved.
  • Liu, Liwei; Herfindal, Lars; Jokela, Jouni; Shishido, Tania Keiko; Wahlsten, Matti; Doskeland, Stein Ove; Sivonen, Kaarina (2014)
  • Jamshidi, Maral; Fagerholm, Rainer; Muranen, Taru A.; Kaur, Sippy; Potdar, Swapnil; Khan, Sofia; Netti, Eliisa; Mpindi, John-Patrick; Yadav, Bhagwan; Kiiski, Johanna I.; Aittomäki, Kristiina; Heikkilä, Päivi; Saarela, Jani; Bützow, Ralf; Blomqvist, Carl; Nevanlinna, Heli (2021)
  • Peltonen, Karita; Colis, Laureen; Liu, Hester; Jaamaa, Sari; Moore, Henna M.; Enback, Juulia; Laakkonen, Pirjo; Vaahtokari, Anne; Jones, Richard J.; af Hallstrom, Taija M.; Laiho, Marikki (2010)
  • Rodrigues, Joana M.; Hassan, May; Freiburghaus, Catja; Eskelund, Christian W.; Geisler, Christian; Räty, Riikka; Kolstad, Arne; Sundstrom, Christer; Glimelius, Ingrid; Gronbaek, Kirsten; Kwiecinska, Anna; Porwit, Anna; Jerkeman, Mats; Ek, Sara (2020)
    Survival for patients diagnosed with mantle cell lymphoma (MCL) has improved drastically in recent years. However, patients carrying mutations in tumour protein p53 (TP53) do not benefit from modern chemotherapy-based treatments and have poor prognosis. Thus, there is a clinical need to identify missense mutations through routine analysis to enable patient stratification. Sequencing is not widely implemented in clinical practice for MCL, and immunohistochemistry (IHC) is a feasible alternative to identify high-risk patients. The aim of the present study was to investigate the accuracy of p53 as a tool to identify patients withTP53missense mutations and the prognostic impact of overexpression and mutations in a Swedish population-based cohort. In total, 317 cases were investigated using IHC and 255 cases were sequenced, enabling analysis of p53 andTP53status among 137 cases divided over the two-cohort investigated. The accuracy of predicting missense mutations from protein expression was 82%, with sensitivity at 82% and specificity at 100% in paired samples. We further show the impact of p53 expression andTP53mutations on survival (hazard ratio of 3 center dot 1 in univariate analysis for both), and the association to risk factors, such as high MCL International Prognostic Index, blastoid morphology and proliferation, in a population-based setting.
  • Raasmaja, Atso; Stenius, Ulla; Ghalali, Aram (2019)
    Juniper (Juniperus communis L.) is a northern coniferous plant generally used as a spice and for nutritional purposes in foods and drinks. It was previously reported that juniper extract (JE) affects p53 activity, cellular stress, and gene expression induced cell death in human neuroblastoma cells. Therefore, the effects of juniper on p53 and Akt signaling was examined further in A549 lung, 22RV1 and DU145 prostate, and HepG2 liver cancer cells using Western blot, confocal microscopy, and MTT analysis. We found that juniper simultaneously decreased cell viability, activated the p53 pathway, and inactivated the PI3K/Akt pathway. The p53 activation was associated with increased nuclear p53 level. Akt was dephosphorylated, and its inactivation was associated with increased levels of PHLPP1 and PHLPP2 phosphatases. Parallel increases of PARP suggest that JE decreased cell viability by activating cell death. In addition, JE potentiated the effects of gemcitabine and 5-fluorouracil anticancer drugs. Thus, JE can activate cell death in different cancer cell lines through p53 and Akt pathways.