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https://www.readbyqxmd.com/read/28737508/targeting-nek2-attenuates-glioblastoma-growth-and-radioresistance-by-destabilizing-histone-methyltransferase-ezh2
#1
Jia Wang, Peng Cheng, Marat S Pavlyukov, Hai Yu, Zhuo Zhang, Sung-Hak Kim, Mutsuko Minata, Ahmed Mohyeldin, Wanfu Xie, Dongquan Chen, Violaine Goidts, Brendan Frett, Wenhao Hu, Hongyu Li, Yong Jae Shin, Yeri Lee, Do-Hyun Nam, Harley I Kornblum, Maode Wang, Ichiro Nakano
Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28735440/new-hypofractionation-radiation-strategies-for-glioblastoma
#2
REVIEW
Melissa Azoulay, Jennifer Shah, Erqi Pollom, Scott G Soltys
PURPOSE OF REVIEW: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with a median survival of less than 2 years despite the standard of care treatment of 6 weeks of chemoradiotherapy. We review the data investigating hypofractionated radiotherapy (HFRT) in the treatment of newly diagnosed GBM. RECENT FINDINGS: Investigators have explored alternative radiotherapy strategies that shorten treatment duration with the goal of similar or improved survival while minimizing toxicity...
September 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28730140/current-advances-in-checkpoint-inhibitors-lessons-from-non-central-nervous-system-cancers-and-potential-for-glioblastoma
#3
REVIEW
Natasha Lakin, Robert Rulach, Stefan Nowicki, Kathreena M Kurian
The adaptive immune system depends on the sequence of antigen presentation, activation, and then inhibition to mount a proportionate response to a threat. Tumors evade the immune response partly by suppressing T-cell activity using immune checkpoints. The use of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1) antibodies counteract this suppression, thereby enhancing the antitumor activity of the immune system. This approach has proven efficacy in melanoma, renal cancer, and lung cancer...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729027/micrornas-as-multifaceted-players-in-glioblastoma-multiforme
#4
Neri Mercatelli, Silvia Galardi, Silvia Anna Ciafrè
Glioblastoma multiforme (GBM) is the most common and inevitably lethal primary brain tumor, with a median survival rate of only 15 months from diagnosis. The current standard treatment involves maximal surgical resection flanked by radiotherapy and chemotherapy with the alkylating agent temozolomide. However, even such aggressive treatment is never curative, and recurrent tumors always arise, commonly in more aggressive, chemo- and radio-resistant forms, leading to untreatable and deadly tumors. MicroRNAs, recognized major players in cancer, are deeply involved in GBM, as shown by more than a decade of studies...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#5
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
July 19, 2017: Radiation Research
https://www.readbyqxmd.com/read/28718993/role-of-fdg-pet-mri-fdg-pet-ct-and-dynamic-susceptibility-contrast-perfusion-mri-in-differentiating-radiation-necrosis-from-tumor-recurrence-in-glioblastomas
#6
Mojgan Hojjati, Chaitra Badve, Vasant Garg, Curtis Tatsuoka, Lisa Rogers, Andrew Sloan, Peter Faulhaber, Pablo R Ros, Leo J Wolansky
BACKGROUND AND PURPOSE: To compare the utility of quantitative PET/MRI, dynamic susceptibility contrast (DSC) perfusion MRI (pMRI), and PET/CT in differentiating radiation necrosis (RN) from tumor recurrence (TR) in patients with treated glioblastoma multiforme (GBM). METHODS: The study included 24 patients with GBM treated with surgery, radiotherapy, and temozolomide who presented with progression on imaging follow-up. All patients underwent PET/MRI and pMRI during a single examination...
July 18, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28708230/short-course-radiotherapy-concomitant-with-temozolomide-in-gbm-patients-a-phase-ii-study
#7
Laura Fariselli, Lucia Cuppini, Paola Gaviani, Marcello Marchetti, Valentina Pinzi, Ida Milanesi, Giorgia Simonetti, Irene Tramacere, Francesco DiMeco, Andrea Salmaggi, Antonio Silvani
PURPOSE: Despite recent advances, the prognosis of glioblastoma (GBM) remains poor. The aim of this study was to assess the efficacy and tolerability of multiple daily fraction radiotherapy performed with multiple temozolomide (TMZ) administrations in newly diagnosed patients with GBM. METHODS: This trial was a prospective, open-label, monocentric, nonrandomized, single arm, phase II study. The primary endpoint was the proportion of progression-free patients at 12 months, and the secondary endpoints were overall survival (OS) and toxicity...
July 8, 2017: Tumori
https://www.readbyqxmd.com/read/28706761/rapidly-fatal-radiation-induced-glioblastoma
#8
Ivy Ng, Char Loo Tan, Tseng Tsai Yeo, Balamurugan Vellayappan
Glioblastoma (GBM) typically occurs as a primary tumour (i.e., primary GBM) and predominantly affects elderly patients. The remaining ~10% occur as a result of malignant progression from lower grade astrocytic tumours (i.e., secondary GBM). Although there are no certain causative environmental agents, prior radiation exposure may play a role. We report on a patient who had been treated six years prior for a vestibular schwannoma with high-dose conventional radiotherapy and subsequently developed a rapidly fatal glioblastoma at the same location...
June 11, 2017: Curēus
https://www.readbyqxmd.com/read/28693823/feasibility-of-hippocampal-avoidance-radiotherapy-for-glioblastoma
#9
K Thippu Jayaprakash, K Wildschut, R Jena
With improvements in survival for good performance status patients and in specific molecular subtypes of glioblastoma, some patients will survive to develop significant neurocognitive dysfunction. This retrospective planning study quantified hippocampal radiation doses in patients with glioblastoma receiving radical chemo-radiotherapy and compared this with the radiation doses that showed clinical correlation with neurocognitive dysfunction, and evaluated the potential for clinically meaningful hippocampal dose reduction using helical TomoTherapy(®)...
July 7, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28693286/bevacizumab-as-a-last-line-treatment-for-glioblastoma-following-failure-of-radiotherapy-temozolomide-and-lomustine
#10
Katharina J Wenger, Marlies Wagner, Se-Jong You, Kea Franz, Patrick N Harter, Michael C Burger, Martin Voss, Michael W Ronellenfitsch, Emmanouil Fokas, Joachim P Steinbach, Oliver Bähr
In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at the first recurrence. Randomized clinical trials at the second or further recurrence following the failure of radiotherapy, temozolomide and lomustine, and retrospective analyses focusing on this specific cohort, are not yet available. A total of 62 patients with glioblastoma who received bevacizumab after the failure of standard care, including radiotherapy, temozolomide and lomustine, were retrospectively identified...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28692129/distortion-free-diffusion-mri-using-an-mri-guided-tri-cobalt-60-radiotherapy-system-sequence-verification-and-preliminary-clinical-experience
#11
Yu Gao, Fei Han, Ziwu Zhou, Minsong Cao, Tania Kaprealian, Mitchell Kamrava, Chenyang Wang, John Neylon, Daniel A Low, Yingli Yang, Peng Hu
PURPOSE: Monitoring tumor response during the course of treatment and adaptively modifying treatment plan based on tumor biological feedback may represent a new paradigm for radiotherapy. Diffusion MRI has shown great promises in assessing and predicting tumor response to radiotherapy. However, the conventional diffusion-weighted single-shot echo-planar-imaging (DW-ssEPI) technique suffers from limited resolution, severe distortion and possibly inaccurate ADC at low field strength. The purpose of this work is to develop a reliable, accurate and distortion-free diffusion MRI technique that is practicable for longitudinal tumor response evaluation and adaptive radiotherapy on a 0...
July 10, 2017: Medical Physics
https://www.readbyqxmd.com/read/28690875/combination-of-palbociclib-and-radiotherapy-for-glioblastoma
#12
Shane Whittaker, Daniel Madani, Swapna Joshi, Sylvia A Chung, Terrance Johns, Bryan Day, Mustafa Khasraw, Kerrie L McDonald
The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28690586/modulations-in-the-peripheral-immune-system-of-glioblastoma-patient-is-connected-to-therapy-and-tumor-progression-a-case-report-from-the-immo-glio-01-trial
#13
Paul F Rühle, Nicole Goerig, Roland Wunderlich, Rainer Fietkau, Udo S Gaipl, Annedore Strnad, Benjamin Frey
Immune responses are important for efficient tumor elimination, also in immune privileged organs such as the brain. Fostering antitumor immunity has therefore become an important challenge in cancer therapy. This cannot only be achieved by immunotherapies as already standard treatments such as radiotherapy and chemotherapy modify the immune system. Consequently, the understanding of how the tumor, the tumor microenvironment, and immune system are modulated by cancer therapy is required for prognosis, prediction, and therapy adaption...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28689368/maximize-surgical-resection-beyond-contrast-enhancing-boundaries-in-newly-diagnosed-glioblastoma-multiforme-is-it-useful-and-safe-a-single-institution-retrospective-experience
#14
Federico Pessina, Pierina Navarria, Luca Cozzi, Anna Maria Ascolese, Matteo Simonelli, Armando Santoro, Elena Clerici, Marco Rossi, Marta Scorsetti, Lorenzo Bello
The extent of surgical resection (EOR) has been recorded as conditioning outcome in glioblastoma multiforme (GBM) patients but no significant improvements were recorded in survival. The study aimed to evaluate the impact of EOR on survival, investigating the role of fluid-attenuated inversion recovery (FLAIR) abnormalities removal. 282 newly diagnosed GBM patients were treated with surgery followed by concurrent and adjuvant chemo-radiotherapy. The EOR was defined as: SUPr, in case of resection amounting to 100% of enhanced and FLAIR areas; gross total (GTR) in case of resection between 90 and 100% of enhanced areas with variable amount of FLAIR abnormalities; sub-total (STR), between 10 and 89%; biopsy (B) <10%...
July 8, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28685138/immunophenotypic-signature-of-primary-glioblastoma-multiforme-a-case-of-extended-progression-free-survival
#15
Puneet Gandhi, Richa Khare, Nitin Garg, Sandeep Sorte
Glioblastoma-multiforme (GBM), the most aggressive glial tumor, has a worldwide age-adjusted incidence ranging from 0.59-3.69/100000 persons. Despite current multimodal-treatment approach, median-survival time and progression-free survival (PFS) remains short. Glioblastomas display a variety of molecular alterations, which necessitates determining which of these have a prognostic significance. This is a case of a 45-year-old patient who presented with progressive slurring of speech and features of raised intracranial pressure...
June 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28677106/expression-and-prognostic-value-of-jam-a-in-gliomas
#16
Ann Mari Rosager, Mia D Sørensen, Rikke H Dahlrot, Henning B Boldt, Steinbjørn Hansen, Justin D Lathia, Bjarne W Kristensen
Gliomas are among the most lethal cancers, being highly resistant to both chemo- and radiotherapy. The expression of junctional adhesion molecule-A (JAM-A) was recently identified on the surface of stem cell-like brain tumor-initiating cells and suggested to function as a unique glioblastoma niche adhesion factor influencing the tumorigenic potential of brain tumor-initiating cells. We have recently identified high JAM-A expression to be associated with poor outcome in glioblastomas, and our aim was to further investigate the expression of JAM-A in gliomas focusing especially on the prognostic value in WHO grade II and III gliomas...
July 4, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28675067/postoperative-neoadjuvant-temozolomide-before-radiotherapy-versus-standard-radiotherapy-in-patients-60-years-or-younger-with-anaplastic-astrocytoma-or-glioblastoma-a-randomized-trial
#17
Annika Malmström, Hans Skovgaard Poulsen, Bjørn Henning Grønberg, Giuseppe Stragliotto, Steinbjørn Hansen, Thomas Asklund, Birgitta Holmlund, Małgorzata Łysiak, Joseph Dowsett, Bjarne Winther Kristensen, Peter Söderkvist, Johan Rosell, Roger Henriksson
INTRODUCTION: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ. PATIENTS AND METHODS: Patients, after surgery for GBM or AA, age ≤60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200 mg/m(2) days 1-5 every 28 days, followed by RT 60 Gy in 30 fractions or RT only...
July 4, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28672945/o-6-methyl-guanine-dna-methyltransferase-methylation-and-idh1-2-mutation-in-small-cell-lung-cancer
#18
Hongyang Lu, Jing Qin, Haimiao Xu, Na Han, Fajun Xie, Weimin Mao
Small cell lung cancer (SCLC) is sensitive to first-line chemotherapy and radiotherapy, but frequently recurs. Temozolomide is a chemotherapeutic drug suitable for the treatment of relapsed SCLC, particularly when brain metastases are present. The response of SCLC to temozolomide may be associated with the methylation status of O(6)-methyl-guanine-DNA methyltransferase (MGMT). Isocitrate dehydrogenase (IDH) mutation is an independent prognostic factor of good outcome in gliomas and appears to be a significant marker of positive chemosensitivity in secondary glioblastoma...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28668896/systemic-intravenous-adoptive-transfer-of-autologous-lymphokine-activated-%C3%AE-%C3%AE-t-cells-improves-temozolomide-induced-lymphopenia-in-patients-with-glioma
#19
Yonehiro Kanemura, Miho Sumida, Yoshiko Okita, Ema Yoshioka, Atsuyo Yamamoto, Daisuke Kanematsu, Yukako Handa, Hayato Fukusumi, Yui Inazawa, A I Takada, Masahiro Nonaka, Shin Nakajima, Kanji Mori, Shigenori Goto, Takashi Kamigaki, Tomoko Shofuda, Shusuke Moriuchi, Mami Yamasaki
In this clinical study, we investigated the safety and clinical usefulness of systemic adoptive immunotherapy using autologous lymphokine-activated αβ T-cells (αβ T-cells), combined with standard therapies, in patients with malignant brain tumors. Twenty-three patients with different malignant brain tumors, consisting of 14 treated with temozolomide (TMZ group) and 9 treated without temozolomide (non-TMZ group), received systemic intravenous injections of αβ T-cells (mean=10.4 injections/patient for the TMZ group, and 4...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28660172/pineal-region-glioblastoma-a-case-report-and-literature-review
#20
Hayley Beacher Stowe, C Ryan Miller, Jing Wu, Dina M Randazzo, Andrew Wenhua Ju
INTRODUCTION: Pineal region glioblastoma multiforme (GBM) is a rare disease entity with a generally poor prognosis. We present a case of a patient with an unresectable pineal region GBM treated with chemoradiation with favorable outcome. CASE BACKGROUND: A 65-year-old patient who was presented with visual symptoms was found to have a pineal region tumor on imaging. A stereotactic biopsy showed a World Health Organization Grade IV GBM, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylated, isocitrate dehydrogenase 1 and 2 wild type...
2017: Frontiers in Oncology
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