Browsing by Subject "PLUS"

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  • Barok, Mark; Le Joncour, Vadim; Martins, Ana; Isola, Jorma; Salmikangas, Marko; Laakkonen, Pirjo; Joensuu, Heikki (2020)
    The majority of HER2-positive breast or gastric cancers treated with T-DM1 eventually show resistance to this agent. We compared the effects of T-DM1 and ARX788, a novel anti-HER2 antibody-drug conjugate, on cell growth and apoptosis in HER2-positive breast cancer and gastric cancer cell lines sensitive to T-DM1, gastric cancer cell lines resistant to T-DM1, HER2-negative breast cancer cell lines, and T-DM1-resistant xenograft models. ARX788 was effective in T-DM1-resistant in vitro and in vivo models of HER2-positive breast cancer and gastric cancer. ARX788 showed a pronounced growth inhibitory effect on all five HER2-positive cell lines tested, of which two gastric cancer cell lines had acquired resistance to T-DM1. ARX788 evoked more apoptotic events compared to T-DM1. While JIMT-1 and RN-87 xenograft tumors progressed on T-DM1 treatment, all such tumors responded to ARX788, and four out of the six JIMT-1 tumors and nine out of the twelve RN-87 tumors disappeared during the ARX788 treatment. Mice treated with ARX788 survived longer than those treated with T-DM1. The data support evaluation of ARX788 in patients with HER2-positive breast cancer or gastric cancer including cancers that progress during T-DM1 therapy.
  • Adam, J.; Adamova, D.; Aggarwal, M. M.; Rinella, G. Aglieri; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Almaraz, J. R. M.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Anielski, J.; Anticic, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshaeuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Brucken, E. J.; Chang, B.; Kim, D. J.; Krizek, F.; Mieskolainen, M. M.; Orava, R.; Rak, J.; Räsänen, S. S.; Snellman, T. W.; Trzaska, W. H. (2016)
    The measurement of prompt D-meson production as a function of multiplicity in p-Pb collisions at TeV with the ALICE detector at root s(NN) the LHC is reported. D-0, D+ and Dau+ mesons are reconstructed via their hadronic decay channels in the centre-of-mass rapidity range -0.96 <y(cms) <0.04 and transverse momentum interval 1 <p(T) <24 GeV/c. The multiplicity dependence of D-meson production is examined by either comparing yields in p-Pb collisions in different event classes, selected based on the multiplicity of produced particles or zero-degree energy, with those in pp collisions, scaled by the number of binary nucleon-nucleon collisions (nuclear modification factor); as well as by evaluating the per-event yields in p-Pb collisions in different multiplicity intervals normalised to the multiplicity-integrated ones (relative yields). The nuclear modification factors for D-0, D+ and D*(+) are consistent with one another. The D-meson nuclear modification factors as a function of the zero-degree energy are consistent with unity within uncertainties in the measured p(T) regions and event classes. The relative D-meson yields, calculated in various p(T) intervals, increase as a function of the charged-particle multiplicity. The results are compared with the equivalent pp measurements at root s = 7 TeV as well as with EPOS 3 calculations.
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2018)
    A search has been performed for heavy resonances decaying to ZZ or ZW in 2l2q final states, with two charged leptons (l = e, mu) produced by the decay of a Z boson, and two quarks produced by the decay of a W or Z boson. The analysis is sensitive to resonances with masses in the range from 400 to 4500 GeV. Two categories are defined based on the merged or resolved reconstruction of the hadronically decaying vector boson, optimized for high- and low-mass resonances, respectively. The search is based on data collected during 2016 by the CMS experiment at the LHC in proton-proton collisions with a center-of-mass energy of root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). No excess is observed in the data above the standard model background expectation. Upper limits on the production cross section of heavy, narrow spin-1 and spin-2 resonances are derived as a function of the resonance mass, and exclusion limits on the production of W' bosons and bulk graviton particles are calculated in the framework of the heavy vector triplet model and warped extra dimensions, respectively.
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2018)
    A search for new physics in events with a Z boson produced in association with large missing transverse momentum at the LHC is presented. The search is based on the 2016 data sample of proton-proton collisions recorded with the CMS experiment at root s = 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1). The results of this search are interpreted in terms of a simplified model of dark matter production via spin-0 or spin-1 mediators, a scenario with a standard-model-like Higgs boson produced in association with the Z boson and decaying invisibly, a model of unparticle production, and a model with large extra spatial dimensions. No significant deviations from the background expectations are found, and limits are set on relevant model parameters, significantly extending the results previously achieved in this channel.
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2019)
    A search for a heavy resonance decaying into a top quark and antiquark (tt) pair is performed using proton-proton collisions at p s = 13TeV. The search uses the data set collected with the CMS detector in 2016, which corresponds to an integrated luminosity of 35.9 fb. The analysis considers three exclusive fi nal states and uses reconstruction techniques that are optimized for top quarks with high Lorentz boosts, which requires the use of nonisolated leptons and jet substructure techniques. No signi fi cant excess of events relative to the expected yield from standard model processes is observed. Upper limits on the production cross section of heavy resonances decaying to a tt pair are calculated. Limits are derived for a leptophobic topcolor Z 0 resonance with widths of 1, 10, and 30%, relative to the mass of the resonance, and exclude masses up to 3.80, 5.25, and 6.65TeV, respectively. Kaluza-Klein excitations of the gluon in the Randall-Sundrum model are excluded up to 4.55TeV. To date, these are the most stringent limits on tt resonances.
  • The CMS collaboration; Sirunyan, A. M.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T. (2018)
    A search is presented for the associated production of a Higgs boson with a top quark pair in the all-jet final state. Events containing seven or more jets are selected from a sample of proton-proton collisions at root s = 13 TeV collected with the CMS detector at the LHC in 2016, corresponding to an integrated luminosity of 35.9 fb(-1). To separate the t (t) over barH signal from the irreducible t (t) over bar + b (b) over bar background, the analysis assigns leading order matrix element signal and background probability densities to each event. A likelihood-ratio statistic based on these probability densities is used to extract the signal. The results are provided in terms of an observed t (t) over barH signal strength relative to the standard model production cross section mu = sigma/sigma(SM), assuming a Higgs boson mass of 125 GeV. The best fit value is (mu) over cap = 0.9 +/- 0.7(stat) +/- 1.3(syst) = 0.9 +/- 1.5 (tot), and the observed and expected upper limits are, respectively, mu <3.8 and <3.1 at 95% confidence levels.
  • Kozlowska, Emilia; Vallius, Tuulia; Hynninen, Johanna; Hietanen, Sakari; Färkkilä, Anniina; Hautaniemi, Sampsa (2019)
    A major issue in oncology is the high failure rate of translating preclinical results in successful clinical trials. Using a virtual clinical trial simulations approach, we present a mathematical framework to estimate the added value of combinatorial treatments in ovarian cancer. This approach was applied to identify effective targeted therapies that can be combined with the platinum-taxane regimen and overcome platinum resistance in high-grade serous ovarian cancer. We modeled and evaluated the effectiveness of three drugs that target the main platinum resistance mechanisms, which have shown promising efficacy in vitro, in vivo, and early clinical trials. Our results show that drugs resensitizing chemoresistant cells are superior to those aimed at triggering apoptosis or increasing the bioavailability of platinum. Our results further show that the benefit of using biomarker stratification in clinical trials is dependent on the efficacy of the drug and tumor composition. The mathematical framework presented herein is suitable for systematically testing various drug combinations and clinical trial designs in solid cancers.