• Bevacizumab treatment induces metabolic adaptation toward anaerobic metabolism in glioblastomas 

      Fack, Fred; Espedal, Heidi; Keunen, Olivier; Golebiewska, Anna; Obad, Nina; Harter, Patrick N.; Mittelbronn, Michel; Bähr, Oliver; Weyerbrock, Astrid; Stuhr, Linda Elin Birkhaug; Miletic, Hrvoje; Sakariassen, Per Øystein; Stieber, Daniel; Rygh, Cecilie Brekke; Lund-Johansen, Morten; Zheng, Liang; Gottlieb, Eyal; Niclou, Simone P.; Bjerkvig, Rolf (Peer reviewed; Journal article, 2015-01)
      Anti-angiogenic therapy in glioblastoma (GBM) has unfortunately not led to the anticipated improvement in patient prognosis. We here describe how human GBM adapts to bevacizumab treatment at the metabolic level. By performing ...
    • Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma 

      Euskirchen, Philipp; Radke, Josefine; Schmidt, Marc Sören; Heuling, Eva Schulze; Kadikowski, Eric; Maricos, Meron; Knab, Felix; Grittner, Ulrike; Zerbe, Norman; Czabanka, Marcus; Dieterich, Christoph; Miletic, Hrvoje; Mørk, Sverre; Koch, Arend; Endres, Matthias; Harms, Christoph (Peer reviewed; Journal article, 2017-09-25)
      The transcription factor ZEB1 has gained attention in tumor biology of epithelial cancers because of its function in epithelial-mesenchymal transition, DNA repair, stem cell biology and tumor-induced immunosuppression, but ...
    • Cellular Host Responses to Gliomas 

      Najbauer, Joseph; Huszthy, Peter Csaba; Barish, Michael E.; Garcia, Elizabeth; Metz, Marianne Z.; Myers, Sarah M.; Gutova, Margarita; Frank, Richard T.; Miletic, Hrvoje; Kendall, Stephen E.; Glackin, Carlotta A.; Bjerkvig, Rolf; Aboody, Karen S. (Peer reviewed; Journal article, 2012-04-23)
      Background: Glioblastoma multiforme (GBM) is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular ...
    • Deciphering the complex role of thrombospondin-1 in glioblastoma development 

      Daubon, Thomas; Léon, Céline; Clarke, Kim; Andrique, Laetitia; Salabert, Laura; Darbo, Elodie; Pineau, Raphael; Guérit, Sylvaine; Maitre, Marlène; Dedieu, Stéphane; Jeanne, Albin; Bailly, Sabine; Feige, Jean-Jacques; Miletic, Hrvoje; Rossi, Marco; Bello, Lorenzo; Falciani, Francesco; Bjerkvig, Rolf; Bikfalvi, Andréas (Peer reviewed; Journal article, 2019-03-08)
      We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased ...
    • Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease 

      Dölle, Christian; Flønes, Irene Hana; Sanchez Nido, Gonzalo; Miletic, Hrvoje; Osuagwu, Nelson; Kristoffersen, Stine; Lilleng, Peer Kåre; Larsen, Jan Petter; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Bindoff, Laurence; Tzoulis, Charalampos (Peer reviewed; Journal article, 2016-11-22)
      Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we ...
    • GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production 

      Mahootchi, Elaheh; Homaei, Selina Cannon; Kleppe, Rune; Winge, Ingeborg; Hegvik, Tor-Arne; Perez, Roberto Megias; Totland, Christian; Mogavero, Floriana; Baumann, Anne; Glennon, Jeffrey Colm; Miletic, Hrvoje; Kursula, Petri; Haavik, Jan (Journal article; Peer reviewed, 2020)
      Carnosine and related β-alanine–containing peptides are believed to be important antioxidants, pH buffers, and neuromodulators. However, their biosynthetic routes and therapeutic potential are still being debated. This ...
    • Interfering with long non-coding RNA MIR22HG processing inhibits glioblastoma progression through suppression of Wnt/β-catenin signalling 

      Han, Mingzhi; Wang, Shuai; Fritah, Sabrina; Wang, Xu; Zhou, Wenjing; Yang, Ning; Ni, Shilei; Huang, Bin; Chen, Anjing; Li, Gang; Miletic, Hrvoje; Thorsen, Frits; Bjerkvig, Rolf; Li, Xingang; Wang, Jian (Peer reviewed; Journal article, 2020)
      Long non-coding RNAs play critical roles in tumour progression. Through analysis of publicly available genomic datasets, we found that MIR22HG, the host gene of microRNAs miR-22-3p and miR-22-5p, is ranked among the most ...
    • Long-term treatment with valganciclovir improves lentiviral suicide gene therapy of glioblastoma 

      Hossain, Jubayer; Latif, Md Abdul; Ystaas, Lars Andreas Rømo; Ninzima, Sandra; Riecken, Kristoffer; Muller, Arnaud; Azuaje, Fransisco; Vareecal Joseph, Justin; Talasila, Krishna Mukharji; Ghimire, Jiwan; Fehse, Boris; Bjerkvig, Rolf; Miletic, Hrvoje (Peer reviewed; Journal article, 2019)
      Background: Suicide gene therapy for malignant gliomas has shown encouraging results in the latest clinical trials. However, prodrug application was most often restricted to short-term treatment (14 days), especially when ...
    • Low expression levels of ATM may substitute for CHEK2 / TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer 

      Knappskog, Stian; Chrisanthar, Ranjan; Løkkevik, Erik; Anker, Gun Birgitta; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Leirvaag, Beryl; Miletic, Hrvoje; Lønning, Per Eystein (Peer reviewed; Journal article, 2012-03-15)
      Introduction: Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNAdamaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and ...
    • Mitochondrial DNA depletion in sporadic inclusion body myositis 

      Bhatt, Padmanabh S.; Tzoulis, Charalampos; Balafkan, Novin; Miletic, Hrvoje; Tran, Gia Tuong Thi; Sanaker, Petter Schandl; Bindoff, Laurence (Peer reviewed; Journal article, 2019)
      Sporadic inclusion body myositis (sIBM) is a late onset disorder of unkown aetiology. Mitochondrial changes such as cytochrome oxidase deficient fibres are a well recognised feature and mitochondrial DNA (mtDNA) deletions ...
    • Molecular pathogenesis of polymerase gamma-related neurodegeneration 

      Tzoulis, Charalampos; Tran, Gia Tuong Thi; Coxhead, Jonathan; Bertelsen, Bjørn; Lilleng, Peer Kåre; Balafkan, Novin; Payne, Brendan; Miletic, Hrvoje; Chinnery, Patrick F.; Bindoff, Laurence (Peer reviewed; Journal article, 2014-07)
      Objective: Polymerase gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neurodegeneration and aging. We studied the molecular mechanisms underlying POLG-related neurodegeneration ...
    • Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology 

      Golebiewska, Anna; Hau, Ann-Christin; Oudin, Anaïs; Stieber, Daniel; Yabo, Yahaya A.; Baus, Virginie; Barthelemy, Vanessa; Klein, Eliane; Bougnaud, Sébastien; Keunen, Olivier; Wantz, May; Michelucci, Alessandro; Neirinckx, Virginie; Muller, Arnaud; Kaoma, Tony; Nazarov, Petr V.; Azuaje, Francisco; De Falco, Alfonso; Flies, Ben; Richart, Lorraine; Poovathingal, Suresh K; Arns, Thais; Grzyb, Kamil; Mock, Andreas; Herold-Mende, Christel; Steino, Anne; Brown, Dennis; May, Patrick; Miletic, Hrvoje; Malta, Tathiane M.; Noushmehr, Houtan; Kwon, Yong-Jun; Jahn, Winnie; Klink, Barbara; Tanner, Georgette; Stead, Lucy F.; Mittelbronn, Michel; Skupin, Alexander; Hertel, Frank; Bjerkvig, Rolf; Niclou, Simone Pierrette (Journal article; Peer reviewed, 2020)
      Patient-based cancer models are essential tools for studying tumor biology and for the assessment of drug responses in a translational context. We report the establishment a large cohort of unique organoids and patient-derived ...
    • PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1 

      Ji, Jianxiong; Ding, Kaikai; Luo, Tao; Xu, Ran; Zhang, Xin; Huang, Bin; Chen, An-Jing; Zhang, Di; Miletic, Hrvoje; Bjerkvig, Rolf; Thorsen, Frits; Wang, Jian; Li, Xingang (Peer reviewed; Journal article, 2019)
      The Hippo signaling pathway controls organ development and is also known, in cancer, to have a tumor suppressing role. Within the Hippo pathway, we here demonstrate, in human gliomas, a functional interaction of a transmembrane ...
    • Pretreatment of glioblastoma with bortezomib potentiates natural killer cell cytotoxicity through TRAIL/DR5 mediated apoptosis and prolongs animal survival 

      Gras Navarro, Andrea; Espedal, Heidi; Vareecal Joseph, Justin; Moncho, Laura Trachsel; Bahador, Marzieh; Gjertsen, Bjørn Tore; Kristoffersen, Einar Klæboe; Simonsen, Anne; Miletic, Hrvoje; Enger, Per Øyvind; Rahman, Mohummad Aminur; Enger, Martha Chekenya (Peer reviewed; Journal article, 2019-07-17)
      Background: Natural killer (NK) cells are potential effectors in anti-cancer immunotherapy; however only a subset potently kills cancer cells. Here, we examined whether pretreatment of glioblastoma (GBM) with the proteasome ...
    • A reproducible brain tumour model established from human glioblastoma biopsies 

      Wang, Jian; Miletic, Hrvoje; Sakariassen, Per Øystein; Huszthy, Peter Csaba; Jacobsen, Hege; Brekkå, Narve; Li, Xingang; Zhao, Peng; Mørk, Sverre; Chekenya, Martha; Bjerkvig, Rolf; Enger, Per Øyvind (Peer reviewed; Journal article, 2009-12-29)
      Background: Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient ...
    • Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study 

      Rahman, Mohummad Aminur; Brekke, Jorunn; Arnesen, Victoria Smith; Hannisdal, Marianne; Navarro, Andrea Gras; Waha, Andreas; Herfindal, Lars; Rygh, Cecilie Brekke; Bratland, Eirik; Brandal, Petter; Haász, Judit; Oltedal, Leif; Miletic, Hrvoje; Lundervold, Arvid; Lie, Stein Atle; Goplen, Dorota; Chekenya, Martha (Journal article; Peer reviewed, 2020)
      Background Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine ...
    • Suicide gene therapy for the treatment of high-grade glioma: past lessons, present trends, and future prospects 

      Hossain, Jubayer; Marchini, Antonio; Fehse, Boris; Bjerkvig, Rolf; Miletic, Hrvoje (Journal article; Peer reviewed, 2020)
      Suicide gene therapy has represented an experimental cancer treatment modality for nearly 40 years. Among the various cancers experimentally treated by suicide gene therapy, high-grade gliomas have been the most prominent ...
    • Surgical debulking promotes recruitment of macrophages and triggers glioblastoma phagocytosis in combination with CD47 blocking immunotherapy 

      Zhu, Huaiyang; Leiss, Lina Wik; Yang, Ning; Rygh, Cecilie Brekke; Mitra, Siddharta S.; Cheshier, Samuel H.; Weissman, Irving L.; Huang, Bin; Miletic, Hrvoje; Bjerkvig, Rolf; Enger, Per Øyvind; Li, Xingang; Wang, Jian (Peer reviewed; Journal article, 2017)
      Surgical resection is a standard component of treatment in the clinical management of patients with glioblastoma multiforme (GBM). However, experimental therapies are rarely investigated in the context of tumor debulking ...
    • Targeting APLN/APLNR improves antiangiogenic efficiency and blunts proinvasive side effects of VEGFA/VEGFR2 blockade in glioblastoma 

      Mastrella, Giorgia; Hou, Mengzhuo; Li, Min; Stöcklein, Veit M.; Zdouc, Nina; Volmar, Marie N.M.; Miletic, Hrvoje; Reinhard, Sören; Herold-Mende, Christel C.; Kleber, Susanne; Eisenhut, Katharina; Gargiulo, Gaetano; Synowitz, Michael; Vescovi, Angelo L.; Harter, Patrick N.; Penninger, Josef M.; Wagner, Ernst; Mittelbronn, Michel; Bjerkvig, Rolf; Hambardzumyan, Dolores; Schüller, Ulrich; Tonn, Jörg Christian; Radke, Josefine; Glass, Rainer; Kälin, Roland E. (Peer reviewed; Journal article, 2019)
      Antiangiogenic therapy of glioblastoma (GBM) with bevacizumab, a VEGFA-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles of the proangiogenic ...
    • Targeting the NG2/CSPG4 Proteoglycan Retards Tumour Growth and Angiogenesis in Preclinical Models of GBM and Melanoma 

      Wang, Jian; Svendsen, Agnete; Kmiecik, Justyna; Immervoll, Heike; Skaftnesmo, Kai Ove; Planagumà, Jesús; Reed, Rolf K.; Bjerkvig, Rolf; Miletic, Hrvoje; Enger, Per Øyvind; Rygh, Cecilie Brekke; Chekenya, Martha (Peer reviewed; Journal article, 2011-07-29)
      Aberrant expression of the progenitor marker Neuron-glia 2 (NG2/CSPG4) or melanoma proteoglycan on cancer cells and angiogenic vasculature is associated with an aggressive disease course in several malignancies including ...