Selected publications Cancer Pharmacology

[1]          A. Segerman, M. Niklasson, C. Haglund, T. Bergström, M. Jarvius, Y. Xie, A. Westermark, D. Sönmez, A. Hermansson, M. Kastemar, Z. Naimaie-Ali, F. Nyberg, M. Berglund, M. Sundström, G. Hesselager, L. Uhrbom, M. Gustafsson, R. Larsson, M. Fryknäs, B. Segerman, and B. Westermark, “Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.,” Cell Rep, vol. 17, no. 11, pp. 2994–3009, Dec. 2016.

[2]          M. Fryknäs, X. Zhang, U. Bremberg, W. Senkowski, M. H. Olofsson, P. Brandt, I. Persson, P. D'Arcy, J. Gullbo, P. Nygren, L. K. Schughart, S. Linder, and R. Larsson, “Iron chelators target both proliferating and quiescent cancer cells.,” Sci Rep, vol. 6, p. 38343, Dec. 2016.

[3]          W. Senkowski, M. Jarvius, J. Rubin, J. Lengqvist, M. G. Gustafsson, P. Nygren, K. Kultima, R. Larsson, and M. Fryknäs, “Large-Scale Gene Expression Profiling Platform for Identification of Context-Dependent Drug Responses in Multicellular Tumor Spheroids.,” Cell Chem Biol, vol. 23, no. 11, pp. 1428–1438, Nov. 2016.

[4]           K.  Blom, P. Nygren, R. Larsson and C.R. Anderssson, ”Predictive Value of Ex Vivo  Chemosensitivity Assays for Individualized Cancer Chemotherapy: A Meta-Analys”.  SLAS Technology, 2017  

[5]           Blom, K.; Nygren, P.; Alvarsson, J.; et al. Ex Vivo Assessment of Drug Activity in Patient Tumor Cells as a Basis for Tailored Cancer Therapy. J. Lab. Autom. 2016, 21, 178–187. 

[6]          W. Senkowski, X. Zhang, M. H. Olofsson, R. Isacson, U. Höglund, M. Gustafsson, P. Nygren, S. Linder, R. Larsson, and M. Fryknäs, “Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer.,” Mol. Cancer Ther., vol. 14, no. 6, pp. 1504–1516, Jun. 2015.

[7]          A. Eriksson, A. Österroos, S. Hassan, J. Gullbo, L. Rickardson, M. Jarvius, P. Nygren, M. Fryknäs, M. Höglund, and R. Larsson, “Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia.,” Blood Cancer J, vol. 5, no. 4, p. e307, Apr. 2015.

[8]          P. Nygren and R. Larsson, “Drug repositioning from bench to bedside: tumour remission by the antihelmintic drug mebendazole in refractory metastatic colon cancer.,” Acta Oncol, vol. 53, no. 3, pp. 427–428, Mar. 2014.

[9]          X. Zhang, M. Fryknäs, E. Hernlund, W. Fayad, A. De Milito, M. H. Olofsson, V. Gogvadze, L. Dang, S. Påhlman, L. A. K. Schughart, L. Rickardson, P. D'Arcy, J. Gullbo, P. Nygren, R. Larsson, and S. Linder, “Induction of mitochondrial dysfunction as a strategy for targeting tumour cells in metabolically compromised microenvironments.,” Nat Commun, vol. 5, p. 3295, 2014.

[10]        P. Nygren, M. Fryknäs, B. Agerup, and R. Larsson, “Repositioning of the anthelmintic drug mebendazole for the treatment for colon cancer.,” J. Cancer Res. Clin. Oncol., vol. 139, no. 12, pp. 2133–2140, Dec. 2013.

[11]        H. Karlsson, M. Fryknäs, R. Larsson, and P. Nygren, “Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system.,” Exp. Cell Res., vol. 318, no. 13, pp. 1577–1585, Aug. 2012.

[12]        P. D'Arcy, S. Brnjic, M. H. Olofsson, M. Fryknäs, K. Lindsten, M. De Cesare, P. Perego, B. Sadeghi, M. Hassan, R. Larsson, and S. Linder, “Inhibition of proteasome deubiquitinating activity as a new cancer therapy.,” Nat. Med., vol. 17, no. 12, pp. 1636–1640, Nov. 2011.

[13] J. Gullbo, M. Fryknäs, L. Rickardson, P. D'Arcy, M. Hägg, M. Wickström, S. Hassan, G. Westman, S. Brnjic, P. Nygren, S. Linder, and R. Larsson, “Phenotype-based drug screening in primary ovarian carcinoma cultures identifies intracellular iron depletion as a promising strategy for cancer treatment.,” Biochem. Pharmacol., vol. 82, no. 2, pp. 139–147, Jul. 2011.

 [14]  Activity of hydrolytic enzymes in tumour cells is a determinant for antitumour  efficacy of the melphalan containing prodrug J1. Gullbo J, Wickström M, Tullberg M, Ehrsson H, Lewensohn R, Nygren P, Luthman K, Larsson R. J Drug Target. 2003 Jul;11(6):355-63. PMID: 14668056

[15] The novel alkylating prodrug J1: diagnosis directed activity profile ex vivo and combination analyses in vitro. Wickström M, Haglund C, Lindman H, Nygren P, Larsson R, Gullbo J. Invest New Drugs. 2008 Jun;26(3):195-204. Epub 2007 Oct 6.

[16] The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan. Wickström M, Viktorsson K, Lundholm L, Aesoy R, Nygren H, Sooman L, Fryknäs M, Vogel LK, Lewensohn R, Larsson R, Gullbo J. Biochem Pharmacol. 2010 May 1;79(9):1281-90. doi: 10.1016/j.bcp.2009.12.022. Epub 2010 Jan 11. PMID: 20067771

[17] First-in-human, phase I/IIa clinical study of the peptidase potentiated alkylator melflufen administered every three weeks to patients with advanced solid tumor malignancies. Berglund Å, Ullén A, Lisyanskaya A, Orlov S, Hagberg H, Tholander B, Lewensohn R, Nygren P, Spira J, Harmenberg J, Jerling M, Alvfors C, Ringbom M, Nordström E, Söderlind K, Gullbo J. Invest New Drugs. 2015 Dec;33(6):1232-41. doi: 10.1007/s10637-015-0299-2. Epub 2015 Nov 10. PMID: 26553306

Selected publications Computational Medicine

[1]           Bäcklin C and Gustafsson MG. Developer Friendly and Computationally Efficient Predictive Modeling without Information Leakage: The emil Package for R. J. Stat. Software 2017 (accepted).

[2]           Kashif M, Andersson C, Hassan S, Karlsson H, Senkowski W, Fryknäs M, Nygren P, Larsson R, Gustafsson MG. In vitro discovery of promising anti-cancer drug combinations using iterative maximisation of a therapeutic index. Sci Rep. 2015 Sep 22;5:14118.

[3]           Österroos A, Kashif M, Haglund C, Blom K, Höglund M, Andersson C, Gustafsson MG, Eriksson A, Larsson R. Combination screening in vitro identifies synergistically acting KP372-1 and cytarabine against acute myeloid leukemia. Biochemical Pharmacology 2016 Oct 15;118:40-49.

[4]           Nordlund J, Bäcklin CL, Zachariadis V, Cavelier L, Dahlberg J, Öfverholm I, Barbany G, Nordgren A, Övernäs E, Abrahamsson J, Flaegstad T, Heyman MM, Jónsson ÓG, Kanerva J, Larsson R, Palle J, Schmiegelow K, Gustafsson MG, Lönnerholm G, Forestier E, Syvänen AC. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia. Clin Epigenetics. 2015 Feb 17;7(1):11.

[5]           Aftab O, Fryknäs M, Hassan S, Nygren P, Larsson R, Hammerling U, Gustafsson MG. Label free quantification of time evolving morphologies using time-lapse video microscopy enables identity control of cell lines and discovery of chemically induced differential activity in iso-genic cell line pairs. Chemometrics and Intelligent Laboratory Systems, 141:24-32, 2015.

[6]           Freyhult E, Gustafsson MG, Strömbergsson H. A Machine Learning Approach to Explain Drug Selectivity to Soluble and Membrane Protein Targets. Molecular Informatics Volume 34, Issue 1, pages 44–52, January 2015.

[7]           Aftab O, Fryknäs M, Hammerling U, Larsson R, Gustafsson MG. Detection of Cell Aggregation and Altered Cell Viability by Automated Label-Free Video Microscopy: A Promising Alternative to Endpoint Viability Assays in High-Throughput Screening. J Biomol Screen. 2015 Mar;20(3):372-81.

[8]           Aftab O, Engskog MK, Haglöf J, Elmsjö A, Arvidsson T, Pettersson C, Hammerling U, Gustafsson MG. NMR Spectroscopy-Based Metabolic Profiling of Drug-Induced Changes In Vitro Can Discriminate between Pharmacological Classes. J Chem Inf Model. 2014 Nov 24;54(11):3251-8.

[9]           Muhammad K, AnderssonC, Åberg M, Nygren P, Sjöblom T, Hammerling U, Larsson L, Gustafsson MG. A Pragmatic Definition of Therapeutic Synergy Suitable for Clinically Relevant In Vitro Multi-Compound Analyses. Molecular Cancer Therapeutics. 2014 Jul;13(7):1964-76.

[10]         Aftab O, Fryknäs M, Zhang X, De Milito A, Hammerling U, Linder S, Larsson R, Gustafsson MG. Label-free detection and dynamic monitoring of drug-induced intracellular vesicle formation enabled using a 2-dimensional matched filter. Autophagy. 2014 Jan 1;10(1):57-69.

[11]         Schaal W, Hammerling U, Gustafsson MG, Spjuth O. Automated QuantMap for rapid quantitative molecular network topology analysis. Bioinformatics. 2013 Sep 15;29(18):2369-70.

[12]         Lundberg M, Buch Thorsen S, Assarsson E, Villablanca A, Tan B, Gee N, Knowles M, Sander Nielsen B, González Couto E, Martin R, Nilsson O, Fermer C, Schlingemann J, Jarle Christensen I, Nielsen H-J, Ekström B, Andersson C, Gustafsson MG, Brunner N, Stenvang J, Fredriksson S: Multiplexed homogeneous proximity ligation assays for high throughput protein biomarker research in serological material. Molecular and Cellular Proteomics Apr;10(4).

[13]         Andersson C, Gustafsson MG, Strömbergsson H. Quantitative Chemogenomics: Machine-Learning Models of Protein-Ligand Interaction (2011). Review. Current Topics in Medicinal Chemistry 11(15):1978-93.

[14]         Xue B, Soeria-Atmadja D, Gustafsson MG, Hammerling U, Dunker AK, Uversky VN.(2011) Abundance and functional roles of intrinsic disorder in allergenic proteins and allergen representative peptides. Proteins 79(9):2595-606.

[15]         Milani L, Lundmark A, Kiialainen A, Nordlund J, Flaegstad T, Forestier E, Heyman M, Jonmundsson G, Kanerva J, Schmiegelow K, Söderhäll S, Gustafsson MG, Lönnerholm G, Syvänen AC. DNA methylation for subtype classification and prediction of treatment outcome in patients with childhood acute lymphoblastic leukemia. Blood. 2010 Feb 11;115(6):1214-25.