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https://www.readbyqxmd.com/read/27921166/outcome-in-unresectable-glioblastoma-mgmt-promoter-methylation-makes-the-difference
#1
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/27904447/long-term-survival-in-glioblastoma-methyl-guanine-methyl-transferase-mgmt-promoter-methylation-as-independent-favourable-prognostic-factor
#2
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/27903792/clinical-effectiveness-of-bevacizumab-in-patients-with-recurrent-brain-tumours-a-population-based-evaluation
#3
REVIEW
Mário L de Lemos, Adeline Markarian, Esther Chan, Kimberly Schaff, Susan Walisser
BACKGROUND: Bevacizumab is an antiangiogenic agent active in patients with recurrent malignant gliomas. However, evidence for its clinical efficacy is relatively limited so that bevacizumab is approved for this indication in Canada and the United States, but not in the European Union. We reviewed the effectiveness of bevacizumab in patients with recurrent brain tumour using a large population database. METHODS: This was a retrospective, multicentre, study conducted at the BC Cancer Agency, a public cancer care organisation for the residents of the Canadian province of British Columbia...
November 30, 2016: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/27903197/upfront-boost-gamma-knife-leading-edge-radiosurgery-to-flair-mri-defined-tumor-migration-pathways-in-174-patients-with-glioblastoma-multiforme-a-15-year-assessment-of-a-novel-therapy
#4
Christopher M Duma, Brian S Kim, Peter V Chen, Marianne E Plunkett, Ralph Mackintosh, Marlon S Mathews, Ryan M Casserly, Gustavo A Mendez, Daniel J Furman, Garrett Smith, Nathan Oh, Chad A Caraway, Ami R Sanathara, Robert O Dillman, Azzurra-Sky Riley, David Weiland, Lian Stemler, Ruslana Cannell, Daniela Alexandru Abrams, Alexa Smith, Christopher M Owen, Burton Eisenberg, Michael Brant-Zawadzki
OBJECTIVE Glioblastoma multiforme (GBM) is composed of cells that migrate through the brain along predictable white matter pathways. Targeting white matter pathways adjacent to, and leading away from, the original contrast-enhancing tumor site (termed leading-edge radiosurgery [LERS]) with single-fraction stereotactic radiosurgery as a boost to standard therapy could limit the spread of glioma cells and improve clinical outcomes. METHODS Between December 2000 and May 2016, after an initial diagnosis of GBM and prior to or during standard radiation therapy and carmustine or temozolomide chemotherapy, 174 patients treated with radiosurgery to the leading edge (LE) of tumor cell migration were reviewed...
December 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27900341/subventricular-zone-associated-glioblastoma-a-call-for-translational-research-to-guide-clinical-decision-making
#5
Andrew W Smith, Bhupesh Parashar, A Gabriella Wernicke
Glioblastoma (GBM) is both the most common and the most devastating primary cancer of the central nervous system, with an expected overall survival in most patients of about 14 months. Despite extensive research, outcomes for GBM have been largely unchanged since the introduction of temozolomide in 2005. We believe that in order to achieve a breakthrough in therapeutic management, we must begin to identify subtypes of GBM, and tailor treatment to best target a particular tumor's vulnerabilities. Our group has recently produced an examination of the clinical outcomes of radiation therapy directed at tumors that contact the subventricular zone (SVZ), the 3-5 mm lateral border of the lateral ventricles that contains the largest collection of neural stem cells in the adult brain...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27894350/gant61-a-gli-inhibitor-sensitizes-glioma-cells-to-the-temozolomide-treatment
#6
Jianlong Li, Jinquan Cai, Shihong Zhao, Kun Yao, Ying Sun, Yongli Li, Lingchao Chen, Ruiyan Li, Xiuwei Zhai, Junhe Zhang, Chuanlu Jiang
BACKGROUND: The aim of this study was to investigate the effect of downregulating Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes of temozolomide (TMZ)-induced effects and explore the molecular mechanisms. METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone and in combination with TMZ in human glioma cell lines. The mRNA and protein expression alterations were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 28, 2016: Journal of Experimental & Clinical Cancer Research: CR
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/27893811/the-inhibition-of-microrna-128-on-igf-1-activating-mtor-signaling-involves-in-temozolomide-induced-glioma-cell-apoptotic-death
#8
Peng-Hsu Chen, Chia-Hsiung Cheng, Chwen-Ming Shih, Kuo-Hao Ho, Cheng-Wei Lin, Chin-Cheng Lee, Ann-Jeng Liu, Cheng-Kuei Chang, Ku-Chung Chen
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death...
2016: PloS One
https://www.readbyqxmd.com/read/27893419/silver-nanoparticles-enhance-the-sensitivity-of-temozolomide-on-human-glioma-cells
#9
Ping Liang, Hongming Shi, Weiguo Zhu, Qunfeng Gui, Ya Xu, Jianfeng Meng, Xiaoyuan Guo, Zhuang Gong, Huaqun Chen
Glioblastoma multiforme (GBM) continues to be associated with a dismal prognosis despite aggressive treatment. Significant efforts are being made to develop new nanotechnology-based therapeutic and diagnostic agents. Nanoparticles can act directly on cancer cells or as drug carriers to enhance the cancer therapeutic effect. In this study, we investigated the effect of silver nanoparticles (AgNPs) on human glioma U251 cells and its role in the combinational use with Temozolomide (TMZ), an imidazotetrazine derivative of the alkylating agent dacarbazine, against glioma cells...
November 22, 2016: Oncotarget
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
#10
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
#11
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
#12
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/27888811/the-role-of-p53-in-cancer-drug-resistance-and-targeted-chemotherapy
#13
REVIEW
Karin Hientz, André Mohr, Dipita Bhakta-Guha, Thomas Efferth
Cancer has long been a grievous disease complicated by innumerable players aggravating its cure. Many clinical studies demonstrated the prognostic relevance of the tumor suppressor protein p53 for many human tumor types. Overexpression of mutated p53 with reduced or abolished function is often connected to resistance to standard medications, including cisplatin, alkylating agents (temozolomide), anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes (tamoxifen) and EGFR-inhibitors (cetuximab)...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888622/quantification-and-expert-evaluation-of-evidence-for-chemopredictive-biomarkers-to-personalize-cancer-treatment
#14
Shruti Rao, Robert A Beckman, Shahla Riazi, Cinthya S Yabar, Simina M Boca, John L Marshall, Michael J Pishvaian, Jonathan R Brody, Subha Madhavan
Predictive biomarkers have the potential to facilitate cancer precision medicine by guiding the optimal choice of therapies for patients. However, clinicians are faced with an enormous volume of often-contradictory evidence regarding the therapeutic context of chemopredictive biomarkers.We extensively surveyed public literature to systematically review the predictive effect of 7 biomarkers claimed to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1-gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide, TOP1-irinotecan/topotecan, and TOP2A-anthracyclines...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880937/prognostic-relevance-of-mirna-155-methylation-in-anaplastic-glioma
#15
Maximilian Georg Schliesser, Rainer Claus, Thomas Hielscher, Christiane Grimm, Dieter Weichenhan, Jonas Blaes, Benedikt Wiestler, Peter Hau, Johannes Schramm, Felix Sahm, Elisa K Weiß, Markus Weiler, Constance Baer, Friederike Schmidt-Graf, Gabriele Schackert, Manfred Westphal, Anne Hertenstein, Patrick Roth, Norbert Galldiks, Christian Hartmann, Torsten Pietsch, Joerg Felsberg, Guido Reifenberger, Michael Christoph Sabel, Frank Winkler, Andreas von Deimling, Christoph Meisner, Peter Vajkoczy, Michael Platten, Michael Weller, Christoph Plass, Wolfgang Wick
The outcome of patients with anaplastic gliomas varies considerably depending on single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH) genes, as well as molecular classifications based on epigenetic or genetic profiles. Remarkably, 98% of the RNA within a cell is not translated into proteins. Of those, especially microRNAs (miRNAs) have been shown not only to have a major influence on physiologic processes but also to be deregulated and prognostic in malignancies.To find novel survival markers and treatment options we performed unbiased DNA methylation screens that revealed 12 putative miRNA promoter regions with differential DNA methylation in anaplastic gliomas...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879513/high-grade-neuroendocrine-carcinoma-of-the-lung-with-carcinoid-morphology-a-study-of-12-cases
#16
Anne Marie Quinn, Anshuman Chaturvedi, Daisuke Nonaka
Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors but with mitotic count >10/2 mm are reported. There were 7 males and 5 females, with age ranging from 56 to 78 years. Four cases were from never-smokers. All tumors showed architectural and cytomorphologic features of carcinoid tumor, including organoid nesting, insular, trabecular, or acinar growth, and tumor cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or lobular growth pattern was also seen...
December 1, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27878252/temozolomide-inhibits-cellular-growth-and-motility-via-targeting-erk-signaling-in-glioma-c6-cells
#17
Yingge Wang, Shan Gao, Weiguang Wang, Jingyan Liang
Temozolomide (TMZ) is an alkylating agent used for the treatment of aggressive forms of brain tumor based on its antitumor actions. However, the exact effect on cancer and the underlying anticancer molecular mechanism of TMZ remain to be elucidated. In the present study, the effects of TMZ on the growth and motility of glioma C6 cells were investigated. MTT and Transwell assays were used to detect cellular growth and motility. The results showed that TMZ inhibited the proliferation, migration and invasion of the glioma C6 cells in vitro, western blot analysis determined that the phosphorylation of extracellular signal‑regulated protein kinase (ERK)1/2 was decreased in the TMZ‑treated cells, compared with the untreated control cells...
November 23, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27876012/phase-i-study-of-low-dose-metronomic-temozolomide-for-recurrent-malignant-gliomas
#18
Eric T Wong, Joshua Timmons, Amy Callahan, Lauren O'Loughlin, Bridget Giarusso, David C Alsop
BACKGROUND: The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects. Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective. METHODS: This phase I study was performed using metronomic temozolomide (mTMZ) at 25 or 50 mg/m(2)/day continuously in 42-day cycles. Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow, analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9 activities in the cerebrospinal fluid (CSF) as surrogates for tumor angiogenesis and invasion, as well as determination of CSF soluble interleukin-2 receptor alpha (sIL-2Rα) levels as a marker of immune modulation...
November 22, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27865821/the-effects-of-tumor-treating-fields-and-temozolomide-in-mgmt-expressing-and-non-expressing-patient-derived-glioblastoma-cells
#19
Paul A Clark, Jordan T Gaal, Joslyn K Strebe, Cheri A Pasch, Dustin A Deming, John S Kuo, H Ian Robins
A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12...
November 16, 2016: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/27863440/patient-derived-glioblastoma-stem-cells-respond-differentially-to-targeted-therapies
#20
Pratik Kanabur, Sujuan Guo, Gary R Simonds, Deborah F Kelly, Robert G Gourdie, Scott S Verbridge, Zhi Sheng
The dismal prognosis of glioblastoma is, at least in part, attributable to the difficulty in eradicating glioblastoma stem cells (GSCs). However, whether this difficulty is caused by the differential responses of GSCs to drugs remains to be determined. To address this, we isolated and characterized ten GSC lines from established cell lines, xenografts, or patient specimens. Six lines formed spheres in a regular culture condition, whereas the remaining four lines grew as monolayer. These adherent lines formed spheres only in plates coated with poly-2-hydroxyethyl methacrylate...
November 16, 2016: Oncotarget
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