Browsing by Subject "AGGRESSIVENESS"

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  • Hirvonen, Outi M.; Leskelä, Riikka-Leena; Gronholm, Lotta; Haltia, Olli; Rissanen, Antti; Tyynela-Korhonen, Kristiina; Rahko, Eeva K.; Lehto, Juho T.; Saarto, Tiina (2019)
    Background: To avoid aggressive treatments at the end-of-life and to provide palliative care (PC), physicians need to terminate futile anti-cancer treatments and define the palliative goal of the treatment in time. This single center study assesses the practices used to make the decision that leads to treatment with a palliative goal, i.e., the PC decision and its effect on anti-cancer treatments at the end of life. Material and methods: Patients with a cancer diagnosis treated in tertiary hospital during 1st January 2013 - 31st December 2014 and deceased by the end of 2014 were identified in the hospital database (N = 2737). Of these patients, 992 were randomly selected for this study. The PC decision was screened from patient records, i.e., termination of cancer-specific treatments and a focus on symptom-centered PC. Results: The PC decision was defined in 82% of the patients during the last year of life (49% >30 days and 33%
  • Laine, Anna-Liisa; Makinen, Hannu (2018)
    The ability of a parasite strain to establish and grow on its host may be drastically altered by simultaneous infection by other parasite strains. However, we still lack an understanding of how life-history allocations may change under coinfection, although life-history correlations are a critical mechanism restricting the evolutionary potential and epidemiological dynamics of pathogens. Here, we study how life-history stages and their correlations change in the obligate fungal pathogen Podosphaera plantaginis under single infection and coinfection scenarios. We find increased pathogen loads under coinfection, but this is not explained by an enhanced performance at any of the life-history stages that constitute infections. Instead, we show that under coinfection the correlation between timing of sporulation and final pathogen load becomes positive. The changes in pathogen life-history allocations leading to more severe infections under coinfection can have far-reaching epidemiological consequences, as well as implication for our understanding of the evolution of virulence.
  • Juurikka, K.; Dufour, A.; Pehkonen, K.; Mainoli, B.; Campioni Rodrigues, P.; Solis, N.; Klein, T.; Nyberg, P.; Overall, C. M.; Salo, T.; Åström, P. (2021)
    Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.