| 1. |
- Bengtson, Johanna, et al.
(författare)
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Inventering av fjälltaggsvampar (Sárcodon) och violgubbe (Gomphus clavatus) i Gävleborgs län 2008
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Åtgärdsprogrammens arter, fjälltaggsvampar (Sárcodon) och violgubbe (Gomphus clavatus), är marklevande storsvampar som kräver levnadsmiljöer med lång skoglig kontinuitet och specifika markförhållanden. En snabb förstörelse av dessa habitat har lett till att arterna blivit mycket sällsynta, vilket återspeglas i rödlistor över hela Europa. Länsstyrelsens inventering är ett led i de åtgärdsprogram som upprättats i Sverige för att bevara landets delpopulationer av de aktuella svamparterna, som utgör en betydande del av Europas populationer. Årets inventering har lett till flera upptäckter. Länets första fynd av den sällsynta lilaköttiga taggsvampen har gjorts på öarna Orarna och Limön (blivande naturreservat) med över nio mycel. Också friluftsområdet Hemlingbyskogen (naturreservat) har visat sig hysa en nationell topplokal, med goda förutsättningar för en utökning av fyndlistan under kommande inventeringshöstar. Totalt har fynd gjorts på nio lokaler, där sammanlagt fyra av åtgärdsprogrammens tio arter har hittats: • koppartaggsvamp Sárcodon lundéllii (VU) (11 mycel) • lilaköttig taggsvamp Sárcodon fuligíneovioláceus (EN) (9 mycel) • skrovlig taggsvamp Sárcodon scabrósus (VU) (2 mycel) • violgubbe Gomphus clavatus (VU) (11 mycel) Växtplatserna utgörs både av skyddade lokaler, som Orarna och Hemlingby, och av lokaler i produktionsmark. Fyra av växtplatserna saknar specifikt områdesskydd. Eftersom svamparnas habitat utgörs av äldre barrskog, i skogsbrukssammanhang avverkningsmogen skog, är upprättandet av skydds- och skötselplaner i många fall mycket brådskande om växtplatserna ska kunna bevaras. Den aktuella inventeringen ger ett kunskapsunderlag som tidigare helt saknats i länet. Detta ger en ny möjlighet till prioritering och planering av skyddsåtgärder av stor betydelse både för åtgärdsprogrammens arter och för den allmänna biodiversiteten i skogslandskapet. 3
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| 2. |
- Svensson, Katrin, et al.
(författare)
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Hypoxia-mediated induction of the polyamine system provides opportunities for tumor growth inhibition by combined targeting of vascular endothelial growth factor and ornithine decarboxylase.
- 2008
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Ingår i: Cancer Research. - 1538-7445. ; 68:22, s. 9291-9301
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia is a hallmark of solid tumors, which may offer opportunities for targeted therapies of cancer; however, the mechanisms that link hypoxia to malignant transformation and tumor progression are not fully understood. Here, we show that up-regulation of the polyamine system promotes cancer cell survival during hypoxic stress. Hypoxia was found to induce polyamine transport and the key enzyme of polyamine biosynthesis, ornithine decarboxylase (ODC), in a variety of cancer cell lines. Increased ODC protein expression was shown in hypoxic, GLUT-1-expressing regions of tumor spheroids and experimental tumors, as well as in clinical tumor specimens. Hypoxic induction of the polyamine system was dependent on antizyme inhibitor (i.e., a key positive regulator of ODC and polyamine transport), as shown by RNA interference experiments. Interestingly, depletion of the polyamines during hypoxia resulted in increased apoptosis, which indicates an essential role of the polyamines in cancer cell adaptation to hypoxic stress. These results were supported by experiments in an in vivo glioma tumor model, showing significantly enhanced antitumor effects of the antiangiogenic, humanized anti-vascular endothelial growth factor (VEGF) antibody bevacizumab when used in combination with the well-established, irreversible inhibitor of ODC, alpha-difluoromethylornithine. Our results provide important insights into the hypoxic stress response in malignant cells and implicate combined targeting of VEGF and ODC as an alternative strategy to treat cancer disease.
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| 3. |
- Welch, Johanna E, et al.
(författare)
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Single chain fragment anti-heparan sulfate antibody targets the polyamine transport system and attenuates polyamine-dependent cell proliferation.
- 2008
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Ingår i: International Journal of Oncology. - 1019-6439. ; 32:4, s. 749-756
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Tidskriftsartikel (refereegranskat)abstract
- The growth-promoting polyamines are polybasic compounds that efficiently enter cancer cells by as yet incompletely defined mechanisms. Strategies to inhibit their internalization may have important implications in the management of tumor disease. Here, we show that cellular binding and uptake of polyamines are inhibited by a single chain variable fragment anti-heparan sulfate (HS) antibody. Polyamine uptake was inhibited in a dose-dependent manner, and was associated with compensatory up-regulation of ornithine decarboxylase (ODC), i.e. the key enzyme of the polyamine biosynthesis pathway. Conversely, depletion of intracellular polyamines by the specific ODC-inhibitor alpha-difluoromethylornithine (DFMO) resulted in increased cellular binding of polyamine and anti-HS antibody. Importantly, anti-HS antibody also efficiently targeted DFMO-induced polyamine uptake, and combined polyamine biosynthesis inhibition by DFMO, and uptake inhibition by anti-HS antibody attenuated tumor cell proliferation in vitro. In conclusion, cell-surface HS proteoglycan is a relevant target for antibody-mediated inhibition of the uptake of polyamines, and polyamine-dependent cell proliferation.
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| 4. |
- Wittrup, Anders, et al.
(författare)
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ScFv antibody-induced translocation of cell-surface heparan sulfate proteoglycan to endocytic vesicles: Evidence for heparan sulfate epitope specificity and role of both syndecan and glypican.
- 2009
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 284:47, s. 32959-32967
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Tidskriftsartikel (refereegranskat)abstract
- Cellular uptake of several viruses and polybasic macromolecules requires the expression of cell-surface heparan sulfate proteoglycan (HSPG) through as yet ill-defined mechanisms. We unexpectedly found that among several cell-surface binding scFv anti-HS antibody (alphaHS) clones only one, AO4B08, efficiently translocated macromolecular cargo to intracellular vesicles through induction of HSPG endocytosis. Interestingly, AO4B08-induced PG internalization was strictly dependent on HS 2-O-sulfation and appeared independent on intact N-sulfation. AO4B08 and HIV-tat, i.e. a well-known cell penetrating peptide, were shown to compete for the internalizing PG population. To obtain a more detailed characterization of this pathway, we have developed a procedure for the isolation of endocytic vesicles by conjugating AO4B08 with superparamagnetic nano-particles. [35S]sulfate-labelled HSPG was found to accumulate in isolated, AO4B08-containing vesicles, providing first biochemical evidence for intact HSPG co-internalization with its ligand. Further analysis revealed the existence of both syndecan, i.e. a transmembrane HSPG, and glycosylphosphatidyl- inositol anchored glypican in purified vesicles. Importantly, internalized syndecan and glypican were found to colocalize in AO4B08-containing vesicles. Our data establish HSPGs as true internalizing receptors of macromolecular cargo, and indicate that the sorting of cell-surface HSPG to endocytic vesicles is determined by a specific HS epitope that can be carried by both syndecan and glypican core protein.
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