Glioblastoma

Publication Title: 
International Journal of Radiation Oncology, Biology, Physics

PURPOSE: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors. METHODS AND MATERIALS: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5. RESULTS: Five daily doses of 1 and 1.5 Gy, and 10 doses of 0.75 and 1 Gy, cured some U-251 MG tumors.

Author(s): 
Ozawa, Tomoko
Faddegon, Bruce A.
Hu, Lily J.
Bollen, Andrew W.
Lamborn, Kathleen R.
Deen, Dennis F.
Publication Title: 
PloS One

BACKGROUND: Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.

Author(s): 
Safdie, Fernando
Brandhorst, Sebastian
Wei, Min
Wang, Weijun
Lee, Changhan
Hwang, Saewon
Conti, Peter S.
Chen, Thomas C.
Longo, Valter D.
Publication Title: 
Epigenetics

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM).

Author(s): 
Pastori, Chiara
Daniel, Mark
Penas, Clara
Volmar, Claude-Henry
Johnstone, Andrea L.
Brothers, Shaun P.
Graham, Regina M.
Allen, Bryce
Sarkaria, Jann N.
Komotar, Ricardo J.
Wahlestedt, Claes
Ayad, Nagi G.
Publication Title: 
Journal of Cellular Biochemistry

There is an urgent need to identify novel therapies for glioblastoma (GBM) as most therapies are ineffective. A first step in this process is to identify and validate targets for therapeutic intervention. Epigenetic modulators have emerged as attractive drug targets in several cancers including GBM. These epigenetic regulators affect gene expression without changing the DNA sequence. Recent studies suggest that epigenetic regulators interact with drivers of GBM cell and stem-like cell proliferation. These drivers include components of the Notch, Hedgehog, and Wingless (WNT) pathways.

Author(s): 
Allen, Bryce K.
Stathias, Vasileios
Maloof, Marie E.
Vidovic, Dusica
Winterbottom, Emily F.
Capobianco, Anthony J.
Clarke, Jennifer
Schurer, Stephan
Robbins, David J.
Ayad, Nagi G.
Publication Title: 
Neuro-Oncology

BACKGROUND: Regulatory T cells (Tregs) are potentially prognostic indicators in patients with glioblastoma. If differences in frequency of Tregs in tumor or blood account for substantial variation in patient survival, then reliably measuring Tregs may enhance treatment selection and improve outcomes. METHODS: We measured Tregs and CD3+ T cells in tumors and blood from 25 patients with newly diagnosed glioblastoma.

Author(s): 
Thomas, Alissa A.
Fisher, Jan L.
Rahme, Gilbert J.
Hampton, Thomas H.
Baron, Udo
Olek, Sven
Schwachula, Tim
Rhodes, C. Harker
Gui, Jiang
Tafe, Laura J.
Tsongalis, Gregory J.
Lefferts, Joel A.
Wishart, Heather
Kleen, Jonathan
Miller, Michael
Whipple, Chery A.
de Abreu, Francine B.
Ernstoff, Marc S.
Fadul, Camilo E.
Publication Title: 
International Journal of Oncology

Metastatic chondrosarcoma of mesenchymal origin is the second most common bone malignancy and does not respond either to chemotherapy or radiation; therefore, the search for new therapies is relevant and urgent. We described recently that tumor growth inhibiting cytostatic proline-rich polypeptide 1, (PRP-1) significantly upregulated tumor suppressor miRNAs, downregulated onco-miRNAs in human chondrosarcoma JJ012 cell line, compared to chondrocytes culture.

Author(s): 
Galoian, Karina
Qureshi, Amir
D'Ippolito, Gianluca
Schiller, Paul C.
Molinari, Marco
Johnstone, Andrea L.
Brothers, Shaun P.
Paz, Ana C.
Temple, H. T.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma and many other cancers. Small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which BET protein inhibition reduces GBM growth is not completely understood.

Author(s): 
Pastori, Chiara
Kapranov, Philipp
Penas, Clara
Peschansky, Veronica
Volmar, Claude-Henry
Sarkaria, Jann N.
Bregy, Amade
Komotar, Ricardo
St Laurent, Georges
Ayad, Nagi G.
Wahlestedt, Claes
Publication Title: 
Kennedy Institute of Ethics Journal

This paper examines the nature of the harm-benefit tradeoff in early clinical research for interventions that involve remote possibility of direct benefit and likelihood of direct harms to research participants with fatal prognoses, by drawing on the example of gene transfer trials for glioblastoma multiforme. We argue that the appeal made by the component approach to clinical equipoise fails to account fully for the nature of the harm-benefit tradeoff-individual harm for social benefit-that would be required to justify such research.

Author(s): 
Nycum, Gillian
Reid, Lynette
Publication Title: 
Oncotarget

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications.

Author(s): 
Kast, Richard E.
Boockvar, John A.
Brüning, Ansgar
Cappello, Francesco
Chang, Wen-Wei
Cvek, Boris
Dou, Q. Ping
Duenas-Gonzalez, Alfonso
Efferth, Thomas
Focosi, Daniele
Ghaffari, Seyed H.
Karpel-Massler, Georg
Ketola, Kirsi
Khoshnevisan, Alireza
Keizman, Daniel
Magné, Nicolas
Marosi, Christine
McDonald, Kerrie
Muñoz, Miguel
Paranjpe, Ameya
Pourgholami, Mohammad H.
Sardi, Iacopo
Sella, Avishay
Srivenugopal, Kalkunte S.
Tuccori, Marco
Wang, Weiguang
Wirtz, Christian R.
Halatsch, Marc-Eric
Publication Title: 
Oncotarget

CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective.

Author(s): 
Kast, Richard E.
Karpel-Massler, Georg
Halatsch, Marc-Eric

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