| 1. |
- Lehtiö, Lari, et al.
(författare)
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Structural basis for inhibitor specificity in human poly(ADP-ribose) polymerase-3.
- 2009
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Ingår i: Journal of medicinal chemistry. - : American Chemical Society (ACS). - 1520-4804 .- 0022-2623. ; 52:9, s. 3108-11
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Tidskriftsartikel (refereegranskat)abstract
- Poly(ADP-ribose) polymerases (PARPs) activate DNA repair mechanisms upon stress- and cytotoxin-induced DNA damage, and inhibition of PARP activity is a lead in cancer drug therapy. We present a structural and functional analysis of the PARP domain of human PARP-3 in complex with several inhibitors. Of these, KU0058948 is the strongest inhibitor of PARP-3 activity. The presented crystal structures highlight key features for potent inhibitor binding and suggest routes for creating isoenzyme-specific PARP inhibitors.
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| 2. |
- Stolz, Claudia, et al.
(författare)
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Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.
- 2009
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Ingår i: Leukemia & Lymphoma. - : Informa UK Limited. - 1029-2403 .- 1042-8194. ; 50, s. 873-885
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.
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| 3. |
- Thell, Arne, et al.
(författare)
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Notes on the systematics, chemistry and distribution of European Parmelia and Punctelia species (lichenized ascomycetes).
- 2008
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Ingår i: Sauteria. ; 15, s. 545-559
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Tidskriftsartikel (refereegranskat)abstract
- Some European species of the genera Parmelia and Punctelia are analysed using molecular, morphological and chemical characters and notes on their distribution are presented. ITS sequences were compared from a total of 31 representative specimens. Parmelia ernstiae and P. serrana form a sister group to P. pinnatifida and P. saxatilis, whereas P. discordans and P. omphalodes are closely related and form a sister group to all former four species. Bootstrap support values from the PAUP and PHYLIP analyses are used to confirm relationships between Parmelia and Punctelia species. Parmelia ernstiae, P. serrana, Punctelia jeckeri and P. subrudecta are reported from additional countries and provinces. Parmelia ernstiae is reported from Bosnia-Herzegovina and Czech Republic for the first time, and P. serrana is new to Germany, Russia and Ukraine. Data on chemistry are collected both from the literature and from our own investigations. The chemical compounds present in Parmelia ernstiae, P. saxatilis and P. serrana were analysed and compared using HPLC. These morphologically similar species are chemically different.
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