Abstract
The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was...Continue Reading
References
Feb 1, 1989·Journal of Neurosurgery·A A GabbaiK Hotleman
Oct 18, 1994·Biochemistry·D BoucherP Denoulet
Oct 3, 1996·The New England Journal of Medicine·R GorlickJ R Bertino
Jan 1, 1996·Stem Cells·J R BertinoD Banerjee
Aug 5, 1999·Journal of Neurosurgery·S HiragaT Yoshimine
Jun 27, 2002·Biochimica Et Biophysica Acta·Debabrata BanerjeeJoseph R Bertino
Jan 15, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrés J M FerreriFranco Cavalli
Sep 25, 2003·Blood·Christine P HansWing C Chan
Oct 8, 2003·Current Pharmaceutical Design·John J McGuire
Jun 16, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lauren E AbreyUNKNOWN International Primary CNS Lymphoma Collaborative Group
Oct 4, 2005·International Journal of Radiation Oncology, Biology, Physics·Peter C O'BrienUNKNOWN Trans-Tasman Radiation Oncology Group
Nov 23, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lauren E AbreyLisa M DeAngelis
Feb 9, 2008·Autophagy·Hiroshi AokiSeiji Kondo
Jan 15, 2010·Leukemia·G J LeclercJ C Barredo
Feb 4, 2010·British Journal of Cancer·M JoergerA J M Ferreri
May 26, 2010·Journal of Neuro-oncology·Daisuke MutaJun-Ichi Kuratsu
Aug 16, 2011·British Journal of Clinical Pharmacology·Markus JoergerAlwin D R Huitema
Feb 1, 2013·Cancer Research·Naoki ShinojimaFrederick F Lang
Mar 29, 2014·Cancer Science·Shigeo AnaiJun-ichi Kuratsu
Apr 12, 2014·International Journal of Clinical Oncology·Keishi MakinoJun-Ichi Kuratsu
Oct 11, 2014·Journal of Neurosurgery. Pediatrics·Naoki ShinojimaJun-Ichi Kuratsu
Apr 12, 2015·World Neurosurgery·Takahiro YamamotoJun-ichi Kuratsu
Feb 26, 2016·Science Translational Medicine·Bernhard MlecnikJérôme Galon
May 10, 2016·Acta Neuropathologica·David N LouisDavid W Ellison