Grete Hasvold

• Rødland, Gro Elise; Hauge, Sissel; Hasvold, Grete; Bay, Lilli Theres Eilertsen; Henriksen-Raabe, Tine Therese & Joel, Mrinal [Vis alle 7 forfattere av denne artikkelen] (2021). Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells. Cancers. ISSN 2072-6694. doi: 10.3390/cancers13153790. Vis sammendrag

  Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

• Krogstad, Veronica; Vethe, Nils Tore; Robertsen, Ida; Hasvold, Grete; Ose, Anne-Marthe Due & Hermann, Monica [Vis alle 12 forfattere av denne artikkelen] (2018). Determination of Tacrolimus Concentration and Protein Expression of P-Glycoprotein in Single Human Renal Core Biopsies. Therapeutic Drug Monitoring. ISSN 0163-4356. 40(3), s. 292–300. doi: 10.1097/FTD.0000000000000510.
• Schive, Simen Walberg; Mirlashari, Mohammad Reza; Hasvold, Grete; Wang, Mengyu; Josefsen, Dag & Gullestad, Hans Petter [Vis alle 10 forfattere av denne artikkelen] (2017). Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets in Vitro and Potentiate Antidiabetic Effect in Vivo. Cell Medicine. ISSN 2155-1790. 9, s. 103–116. doi: 10.3727/215517917X693401.
• Holm, Kristine Lillebø; Syljuåsen, Randi G.; Hasvold, Grete; Alsøe, Lene; Nilsen, Hilde Loge & Ivanauskiene, Kristina [Vis alle 13 forfattere av denne artikkelen] (2017). TLR9 stimulation of B-cells induces transcription of p53 and prevents spontaneous and irradiation-induced cell death independent of DNA damage responses. Implications for Common variable immunodeficiency. PLOS ONE. ISSN 1932-6203. 12(10). doi: 10.1371/journal.pone.0185708. Fulltekst i vitenarkiv
• Hauge, Sissel; Naucke, Christian; Hasvold, Grete; Joel, Mrinal; Rødland, Gro Elise & Juzenas, Petras [Vis alle 8 forfattere av denne artikkelen] (2017). Combined inhibition of Wee1 and Chk1 gives synergistic DNA damage in S-phase due to distinct regulation of CDK activity and CDC45 loading. OncoTarget. ISSN 1949-2553. 8(7), s. 10966–10979. doi: 10.18632/oncotarget.14089.
• Hasvold, Grete; Lund-Andersen, Christin; Lando, Malin; Patzke, Sebastian; Hauge, Sissel & Suo, Zhenhe [Vis alle 8 forfattere av denne artikkelen] (2016). Hypoxia-induced alterations of G2 checkpoint regulators. Molecular Oncology. ISSN 1574-7891. 10(5), s. 764–773. doi: 10.1016/j.molonc.2015.12.015.
• Syljuåsen, Randi G.; Hasvold, Grete; Hauge, Sissel & Helland, Åslaug (2015). Targeting lung cancer through inhibition of checkpoint kinases. Frontiers in Genetics. ISSN 1664-8021. 6. doi: 10.3389/fgene.2015.00070.
• Hasvold, Grete; Nahse-Kumpf, Viola; Tkacz-Stachowska, Kinga Magda; Rofstad, Einar K & Syljuåsen, Randi G. (2013). The Efficacy of CHK1 Inhibitors Is Not Altered by Hypoxia, but Is Enhanced after Reoxygenation. Molecular Cancer Therapeutics. ISSN 1535-7163. 12(5), s. 705–716. doi: 10.1158/1535-7163.MCT-12-0879.
• Halle, Cathinka Lønning; Andersen, Erlend K F; Lando, Malin; Aarnes, Eva-Katrine; Hasvold, Grete & Holden, Marit [Vis alle 12 forfattere av denne artikkelen] (2012). Hypoxia-induced gene expression in chemoradioresistant cervical cancer revealed by dynamic contrast enhanced MRI. Cancer Research. ISSN 0008-5472. 72(20), s. 5285–5295. doi: 10.1158/0008-5472.CAN-12-1085. Vis sammendrag

  Knowledge of the molecular background of functional magnetic resonance (MR) images is required to fully exploit their potential in cancer management. We explored the prognostic impact of dynamic contrast-enhanced MR imaging (DCE-MRI) parameters in cervical cancer combined with global gene expression data to reveal their underlying molecular phenotype and construct a representative gene signature for the relevant parameter. On the basis of 78 patients with cervical cancer subjected to curative chemoradiotherapy, we identified the prognostic DCE-MRI parameter ABrix by pharmacokinetic analysis of pretreatment images based on the Brix model, in which tumors with low ABrix appeared to be most aggressive. Gene set analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between ABrix and the hypoxia gene sets, whereas gene sets related to other tumor phenotypes were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including both targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response, were the most significant. In the remaining 32 tumors, low ABrix was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. On the basis of the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low ABrix was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Our findings reveal the molecular basis of an aggressive hypoxic phenotype and suggest the use of DCE-MRI to noninvasively identify patients with hypoxia-related chemoradioresistance.

• Petersen, L.; Hasvold, Grete; Lukas, J.; Bartek, J & Syljuåsen, Randi (2010). p53-dependent G(1) arrest in 1st or 2nd cell cycle may protect human cancer cells from cell death after treatment with ionizing radiation and Chk1 inhibitors. Cell Proliferation. ISSN 0960-7722. 43(4), s. 365–371. doi: 10.1111/j.1365-2184.2010.00685.x.
• Landsverk, Helga Bjarnason; Mora-Bermúdez, Felipe; Landsverk, Ole J. B.; Hasvold, Grete; Naderi, Soheil & Bakke, Oddmund [Vis alle 10 forfattere av denne artikkelen] (2010). The protein phosphatase 1 regulator PNUTS is a new component of the DNA damage response. EMBO Reports. ISSN 1469-221X. 11(11), s. 868–875. doi: 10.1038/embor.2010.134.

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• Ose, Anne M; Krogstad, Veronica; Hasvold, Grete; Robertsen, Ida; Egeland, Erlend Johannessen & Hermann, Monica [Vis alle 9 forfattere av denne artikkelen] (2017). Optimalisering av metode for kvantifisering av CYP3A5 og P_glykoprotein i små nyrebiopsier.
• Vu, Martin; Krogstad, Veronica; Johnson, Line Kristin; Angeles, Philip Carlo S; Hasvold, Grete & Hermann, Monica [Vis alle 13 forfattere av denne artikkelen] (2017). Effect of low calorie diet on the absolute bioavailability of midazolam in patients with severe obesity.
• Landsverk, Helga Bjarnason; Mora-Bermúdez, Felipe; Landsverk, Ole J. B.; Hasvold, Grete; Naderi, Soheil & Bakke, Oddmund [Vis alle 10 forfattere av denne artikkelen] (2010). The protein phosphatase 1 regulator PNUTS is a novel component of the DNA damage response.
• Landsverk, Helga Bjarnason; Mora-Bermudez, Felipe; Landsverk, Ole J. B.; Hasvold, Grete; Naderi, Soheil & Bakke, Oddmund [Vis alle 10 forfattere av denne artikkelen] (2009). PP1 nuclear targeting subunit (PNUTS/p99/R111/CAT53) is an integral part of the G2 DNA damage checkpoint.

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