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https://www.readbyqxmd.com/read/27923831/glioblastoma-therapy-can-be-augmented-by-targeting-idh1-mediated-nadph-biosynthesis
#1
Daniel R Wahl, Joseph Dresser, Kari Wilder-Romans, Joshua D Parsels, Shuang G Zhao, Mary Davis, Lili Zhao, Maureen Kachman, Stefanie Wernisch, Charles F Burant, Meredith A Morgan, Felix Y Feng, Corey Speers, Costas A Lyssiotis, Theodore S Lawrence
NADPH is a critical reductant needed in cancer cells to fuel the biosynthesis of deoxynucleotides and antioxidant and to sustain stress-survival responses after radiation-induced DNA damage. Thus, one rational strategy to attack cancer cells is to target their heavy reliance on NADPH. Here we report that the isocitrate dehydrogenase IDH1 is the most strongly upregulated NADPH-producing enzyme in glioblastoma (GBM). IDH1 silencing in GBM cells reduced levels of NADPH, deoxynucleotides and glutathione and increased their sensitivity to radiation-induced senescence...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27921166/outcome-in-unresectable-glioblastoma-mgmt-promoter-methylation-makes-the-difference
#2
Niklas Thon, Jun Thorsteinsdottir, Sabina Eigenbrod, Ulrich Schüller, Jürgen Lutz, Simone Kreth, Claus Belka, Jörg-Christian Tonn, Maximilian Niyazi, Friedrich Wilhelm Kreth
In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008...
December 5, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27918194/first-report-of-tumor-treating-fields-use-in-combination-with-bevacizumab-in-a-pediatric-patient-a-case-report
#3
Daniel O'Connell, Violet Shen, William Loudon, Daniela A Bota
We report the first case of a pediatric patient with glioblastoma (GBM; WHO grade IV astrocytoma) successfully treated with tumor treating fields (TTF). The patient was diagnosed with GBM when 13 years of age and progressed through surgical resection, radiotherapy and chemotherapy. Discrete tumor growth visualized on MRI with stable neurological examination was monitored for 6 months with subsequent stable disease observed radiographically and clinically for 7 months while adherent to Optune(®) (TTF). TTF thereby played a role in forestalling recurrent GBM growth in this young woman for 7 months without significant adverse effects...
December 5, 2016: CNS Oncology
https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#4
Nan Liu, Lei Zhang, Zhen Wang, Yingduan Cheng, Pengxing Zhang, Xin Wang, Weihong Wen, Hongwei Yang, Hui Liu, Weilin Jin, Yongsheng Zhang, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27904447/long-term-survival-in-glioblastoma-methyl-guanine-methyl-transferase-mgmt-promoter-methylation-as-independent-favourable-prognostic-factor
#5
Uros Smrdel, Mara Popovic, Matjaz Zwitter, Emanuela Bostjancic, Andrej Zupan, Viljem Kovac, Damjan Glavac, Drago Bokal, Janja Jerebic
BACKGROUND: In spite of significant improvement after multi-modality treatment, prognosis of most patients with glioblastoma remains poor. Standard clinical prognostic factors (age, gender, extent of surgery and performance status) do not clearly predict long-term survival. The aim of this case-control study was to evaluate immuno-histochemical and genetic characteristics of the tumour as additional prognostic factors in glioblastoma. PATIENTS AND METHODS: Long-term survivor group were 40 patients with glioblastoma with survival longer than 30 months...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27903708/astrocyte-elevated-gene-1-regulates-beta-catenin-signaling-to-maintain-glioma-stem-like-stemness-and-self-renewal
#6
Bin Hu, Luni Emdad, Timothy P Kegelman, Xue-Ning Shen, Swadesh K Das, Devanand Sarkar, Paul B Fisher
: Glioblastoma multiforme (GBM) is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSCs) are responsible for GBM escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers including GBM, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology...
November 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27893927/model-averaged-double-robust-estimation
#7
Matthew Cefalu, Francesca Dominici, Nils Arvold, Giovanni Parmigiani
Researchers estimating causal effects are increasingly challenged with decisions on how to best control for a potentially high-dimensional set of confounders. Typically, a single propensity score model is chosen and used to adjust for confounding, while the uncertainty surrounding which covariates to include into the propensity score model is often ignored, and failure to include even one important confounder will results in bias. We propose a practical and generalizable approach that overcomes the limitations described above through the use of model averaging...
November 28, 2016: Biometrics
https://www.readbyqxmd.com/read/27893327/radiation-therapy-for-glioblastoma-american-society-of-clinical-oncology-clinical-practice-guideline-endorsement-of-the-american-society-for-radiation-oncology-guideline
#8
Erik P Sulman, Nofisat Ismaila, Terri S Armstrong, Christina Tsien, Tracy T Batchelor, Tim Cloughesy, Evanthia Galanis, Mark Gilbert, Vinai Gondi, Mary Lovely, Minesh Mehta, Matthew P Mumber, Andrew Sloan, Susan M Chang
Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on radiation therapy for glioblastoma. Because of its relevance to the ASCO membership, ASCO reviewed the guideline and applied a set of procedures and policies used to critically examine guidelines developed by other organizations. Methods The ASTRO guideline on radiation therapy for glioblastoma was reviewed for developmental rigor by methodologists. An ASCO endorsement panel updated the literature search and reviewed the content and recommendations...
November 28, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27889835/valproic-acid-reduces-hair-loss-and-improves-survival-in-patients-receiving-temozolomide-based-radiation-therapy-for-high-grade-glioma
#9
Shinichi Watanabe, Yui Kuwabara, Satoshi Suehiro, Daisuke Yamashita, Mamoru Tanaka, Akihiro Tanaka, Shiro Ohue, Hiroaki Araki
PURPOSE: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma...
November 26, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27889247/cutaneous-invasive-aspergillosis-in-a-patient-with-glioblastoma-receiving-long-term-temozolomide-and-corticosteroid-therapy
#10
Takashi Ikeda, Jun Suzuki, Masataro Norizuki, Taro Okabe, Tsubasa Onishi, Teppei Sasahara, Masaki Toshima, Hidenori Yokota, Shuji Hatakeyama, Yuji Morisawa
Glioblastoma is an aggressive brain tumor that requires multidisciplinary treatment including adjuvant radiotherapy, chemotherapy, and adjunct corticosteroids. Temozolomide is a commonly used chemotherapy drug and frequently causes lymphocytopenia. We describe the case of a 67-year-old woman with cutaneous invasive aspergillosis who had received long-term temozolomide and corticosteroid therapy for glioblastoma. She presented with multiple indurations, erythema, and purpura, some of which produced purulent discharge, in the anterior abdomen...
November 23, 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/27867925/a-stable-secondary-gliosarcoma-with-extensive-systemic-metastases-a-case-report
#11
Tae-Min Choi, Young-Jun Cheon, Tae-Young Jung, Kyung-Hwa Lee
A 63-year-old man complained of intermittent motor weakness of his arm. The magnetic resonance image (MRI) of his brain displayed a high signal lesion in right cingulate gyrus on T2 weighted image. One year later, he showed a stuporous mental status with repeated seizures, and the follow-up brain MRI showed heterogeneously enhanced mass associated with bleeding. He was treated with surgery and radiotherapy for secondary glioblastomas in right cingulate gyrus. One year more later, a mass recurred on the left frontal base, and gliosarcoma was diagnosed...
October 2016: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/27867119/glioblastoma-secondary-to-meningioma-a-case-report-and-literature-review
#12
Pauline Sahuc, Christophe Joubert, Anh-Tuan Nguyen, Bernard Fouet, Delphine Wybrecht, Anthony Faivre, Philippe Alla, Arnaud Dagain
BACKGROUND: The pathophysiologies underlying meningioma and glioma are quite distinct. The coexistence of those two lesions in a same patient is rare, and that at the same location is even more exceptional. CASE DESCRIPTION: We report a case of a 79-year-old man initially presenting a meningioma that was treated by complete excision of the lesion. The patient had two relapses at the same site in which glioblastoma was confirmed histopathologically. CONCLUSIONS: Glial transformation meningiomas remains a contentious issue, with coincidental occurrence being the most prevalent explanation...
November 17, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27864508/radiotherapy-using-imrt-boosts-after-hyperbaric-oxygen-therapy-with-chemotherapy-for-glioblastoma
#13
Katsuya Yahara, Takayuki Ohguri, Hiroki Udono, Junkoh Yamamoto, Kyosuke Tomura, Toshihiro Onoda, Hajime Imada, Shigeru Nishizawa, Yukunori Korogi
The purpose of this study was to evaluate the feasibility and efficacy of radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma. Twenty-four patients with glioblastoma were treated with the combined therapy, which was RT using IMRT boosts after HBO with chemotherapy, and were retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the surrounding edema, including an additional 1...
November 17, 2016: Journal of Radiation Research
https://www.readbyqxmd.com/read/27863310/cyclin-dependent-kinase-2-promotes-tumor-proliferation-and-induces-radio-resistance-in-glioblastoma
#14
Jia Wang, Tong Yang, Gaofeng Xu, Hao Liu, Chunying Ren, Wanfu Xie, Maode Wang
Accumulating evidence indicates that CDK2 promotes hyperproliferation and is associated to poor prognosis in multiple cancer cells. However, the physiological role of CDK2 in GBM and the biological mechanism still remains unclear. In this study, we identified that CDK2 expression was significantly enriched in GBM tumors compared with normal brain. Additionally, CDK2 was functionally required for tumor proliferation and its expression was associated to poor prognosis in GBM patients. Mechanically, CDK2 induced radio resistance in GBM cells and CDK2 knock down increased cell apoptosis when combined with radiotherapy...
December 2016: Translational Oncology
https://www.readbyqxmd.com/read/27845656/personalized-radiotherapy-planning-based-on-a-computational-tumor-growth-model
#15
Matthieu Le, Herve Delingette, Jayashree Kalpathy-Cramer, Elizabeth R Gerstner, Tracy Batchelor, Jan Unkelbach, Nicholas Ayache
In this article, we propose a proof of concept for the automatic planning of personalized radiotherapy for brain tumors. A computational model of glioblastoma growth is combined with an exponential cell survival model to describe the effect of radiotherapy. The model is personalized to the magnetic resonance images (MRIs) of a given patient. It takes into account the uncertainty in the model parameters, together with the uncertainty in the MRI segmentations. The computed probability distribution over tumor cell densities, together with the cell survival model, is used to define the prescription dose distribution, which is the basis for subsequent Intensity Modulated Radiation Therapy (IMRT) planning...
November 8, 2016: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/27834803/advance-care-planning-in-glioblastoma-patients
#16
REVIEW
Lara Fritz, Linda Dirven, Jaap C Reijneveld, Johan A F Koekkoek, Anne M Stiggelbout, H Roeline W Pasman, Martin J B Taphoorn
Despite multimodal treatment with surgery, radiotherapy and chemotherapy, glioblastoma is an incurable disease with a poor prognosis. During the disease course, glioblastoma patients may experience progressive neurological deficits, symptoms of increased intracranial pressure such as drowsiness and headache, incontinence, seizures and progressive cognitive dysfunction. These patients not only have cancer, but also a progressive brain disease. This may seriously interfere with their ability to make their own decisions regarding treatment...
November 8, 2016: Cancers
https://www.readbyqxmd.com/read/27829215/rsk2-activity-mediates-glioblastoma-invasiveness-and-is-a-potential-target-for-new-therapeutics
#17
Florian J Sulzmaier, Shirley Young-Robbins, Pengfei Jiang, Dirk Geerts, Amanda M Prechtl, Michelle L Matter, Santosh Kesari, Joe W Ramos
In glioblastoma (GBM), infiltration of primary tumor cells into the normal tissue and dispersal throughout the brain is a central challenge to successful treatment that remains unmet. Indeed, patients respond poorly to the current therapies of tumor resection followed by chemotherapy with radiotherapy and have only a 16-month median survival. It is therefore imperative to develop novel therapies. RSK2 is a kinase that regulates proliferation and adhesion and can promote metastasis. We demonstrate that active RSK2 regulates GBM cell adhesion and is essential for cell motility and invasion of patient-derived GBM neurospheres...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826681/role-of-surgical-resection-in-recurrent-glioblastoma-prognostic-factors-and-outcome-evaluation-in-an-observational-study
#18
Federico Pessina, Pierina Navarria, Luca Cozzi, Stefano Tomatis, Marco Riva, Anna Maria Ascolese, Armando Santoro, Matteo Simonelli, Lorenzo Bello, Marta Scorsetti
The role of surgical resection in progressive or recurrent glioblastoma multiforme (GBM) lack of high level of evidence. The aim of this evaluation was to assess the role of surgical resection in relapsing GBM, in relation to the extent of surgical resection (EOR) and the amount of residual tumor volume (RTV). Among patients treated for newly diagnosed GBM between September 2008-December 2014, 64 patients with recurrent GBM were included in this retrospective evaluation. All patients underwent surgical resection followed by adjuvant treatments, chemotherapy and/or radiotherapy Results were evaluated in terms of local control (LC) rate, progression free survival (PFS) and patients overall survival (OS)...
November 8, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27819521/microrna-326-sensitizes-human-glioblastoma-cells-to-curcumin-via-the-shh-gli1-signaling-pathway
#19
Shi Yin, Wenzhong Du, Feng Wang, Bo Han, Yuqiong Cui, Dongbo Yang, Hui Chen, Daming Liu, Xing Liu, Chuanlu Jiang
Glioblastoma multiforme is the most malignant and common brain tumor in adults and is characterized by poor survival and high resistance to chemotherapy and radiotherapy. Among the new chemotherapy drugs, curcumin, a popular dietary supplement, has proven to have a potent anticancer effect on a variety of cancer cell types; however, it remains difficult to achieve a satisfactory therapeutic effect with curcumin using the traditional single-drug treatment. In this study, we found that expression of miR-326, a tumor suppressor microRNA in various tumor types, resulted in a marked increase of curcumin-induced cytotoxicity and apoptosis and a decrease of proliferation and migration in glioma cells...
November 7, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27816029/impact-of-timing-of-radiotherapy-in-patients-with-newly-diagnosed-glioblastoma
#20
David M Randolph, Emory R McTyre, Anna K Paulsson, Jordan A Holmes, William H Hinson, Glenn J Lesser, Roy Strowd, Hui-Wen Lo, Adrian W Laxton, Stephen B Tatter, Waldemar Debinski, Michael D Chan
OBJECTIVE: To further evaluate if a delay in the start of radiation therapy (RT) affects patient outcomes for glioblastoma (GBM). PATIENTS AND METHODS: From May 1999 to May 2010, a total of 161 patients underwent surgery followed by RT for GBM. We assessed overall survival (OS) and progression free survival (PFS), stratified by extent of surgical resection. Included in the analysis were genomic predictors of progression. RESULTS: Median time from surgery to start of RT was 20days for biopsy alone, 28days for subtotal resection (STR) and 28days for gross total resection (GTR)...
December 2016: Clinical Neurology and Neurosurgery
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