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D P N Gonçalves, D M Park, T L Schmidt, C Werner
Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs) were used to target the models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS)...
March 20, 2018: Biomaterials Science
Toshihiko Wakabayashi, Atsushi Natsume, Junki Mizusawa, Hiroshi Katayama, Haruhiko Fukuda, Minako Sumi, Ryo Nishikawa, Yoshitaka Narita, Yoshihiro Muragaki, Takashi Maruyama, Tamio Ito, Takaaki Beppu, Hideo Nakamura, Takamasa Kayama, Shinya Sato, Motoo Nagane, Kazuhiko Mishima, Yoko Nakasu, Kaoru Kurisu, Fumiyuki Yamasaki, Kazuhiko Sugiyama, Takanori Onishi, Yasuo Iwadate, Mizuhiko Terasaki, Hiroyuki Kobayashi, Akira Matsumura, Eiichi Ishikawa, Hikaru Sasaki, Akitake Mukasa, Takayuki Matsuo, Hirofumi Hirano, Toshihiro Kumabe, Nobusada Shinoura, Naoya Hashimoto, Tomokazu Aoki, Akio Asai, Tatsuya Abe, Atsuo Yoshino, Yoshiki Arakawa, Kenichiro Asano, Koji Yoshimoto, Soichiro Shibui
PURPOSE: This study explored the superiority of temozolomide (TMZ) + interferonβ (IFNβ) to standard TMZ as treatment for newly diagnosed glioblastoma (GBM) via randomized phase II screening design. EXPERIMENTAL DESIGN: Eligibility criteria included histologically proven GBM, with 50% of the tumor located in supratentorial areas, without involvement of the optic, olfactory nerves, and pituitary gland and without multiple lesions and dissemination. Patients in the TMZ + radiotherapy (RT) arm received RT (2...
March 20, 2018: Journal of Neuro-oncology
Érika Cosset, Sara M Weis, David A Cheresh
No abstract text is available yet for this article.
January 2018: Oncoscience
Kai Huang, Chuan Fang, Kaikai Yi, Xing Liu, Hongzhao Qi, Yanli Tan, Junhu Zhou, Ying Li, Mingyang Liu, Yuqing Zhang, Jingxuan Yang, Jianning Zhang, Min Li, Chunsheng Kang
Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in various malignancies. However, the function of PTRF in tumor progression remains controversial, and its role in glioma is poorly understood. In this study, we report that PTRF is associated with malignancy grade and poor prognosis in glioma patients...
2018: Theranostics
Hung-Chen Wang, Yu-Tsai Lin, Wei-Che Lin, Ren-Wen Ho, Yu-Jun Lin, Nai-Wen Tsai, Jih-Tsun Ho, Cheng-Hsien Lu
BACKGROUND: A standard post-concomitant radiochemotherapy involving adjuvant temozolomide (TMZ) was stopped after 6 cycles for high-grade gliomas (HGG). Several studies demonstrated that prolonged TMZ treatment increased survival for these patients. METHODS: This retrospective study aimed to compare changes in tumor volume during and after adjuvant TMZ treatment and overall survival (OS). RESULTS: There were 90 patients were administered adjuvant TMZ treatment...
March 16, 2018: World Neurosurgery
Chad A Glenn, Cordell M Baker, Andrew K Conner, Josh D Burks, Phillip A Bonney, Robert G Briggs, Adam D Smitherman, James D Battiste, Michael E Sughrue
BACKGROUND: Resection of the T1 contrast-enhancing portion of glioblastoma has been shown to increase patient survival though it is not well-known if GBM resection beyond these boundaries has an additional survival benefit. OBJECTIVE: In this study, we examined the effect of resecting the enhancement and a margin of brain tissue surrounding the enhancement in patients with glioblastoma of the temporal lobe. METHODS: We identified 32 consecutive patients with temporal lobe glioblastoma who underwent initial resection between 2012 and 2015...
March 16, 2018: World Neurosurgery
Hyojin Eom, Neha Kaushik, Ki-Chun Yoo, Jin-Kyoung Shim, Munjin Kwon, Mi-Young Choi, Taeyoung Yoon, Seok-Gu Kang, Su-Jae Lee
Receptor tyrosine kinase Mer (MerTK) has been shown to be highly expressed in Glioblastoma multiforme (GBM) in comparison to its healthy counterpart and is implicated in brain tumorigenesis. Clarifying the underlying mechanism of MerTK induced invasiveness would result in novel strategies to improve patient's response to chemotherapeutics. In vitro and in vivo assays were performed to examine the functional role of cancer stem sell (CSC) maintenance in MerTK associated invasiveness. In this article, we demonstrate that apart from GBM cells, MerTK is also upregulated in GBM stem-like cells and associated with an increased infiltrative potential of brain tumors in vivo...
March 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Vesna Nikolov, Miodrag Stojanovic, Aleksandar Kostic, Misa Radisavljevic, Natasa Simonovic, Boban Jelenkovic, Luka Berilazic
PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive malignant tumor in the brain and no therapy can achieve full recovery/cure. The aim of this study was to identify which factors could improve the survival of operated patients, and to determine which kind of therapy was most successful. METHODS: The study was conducted at the Clinic for Neurosurgery in Nis, Clinical Centre Nis and the Oncology Institute, Clinical Center Nis. A cohort of patients who underwent surgery between January 2013 and December 2015 was studied and continuous monitoring of survival lasted until June 2017...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Li-Yun Fann, Ying Chen, Da-Chen Chu, Shao-Ju Weng, Heng-Cheng Chu, Alexander T H Wu, Jiann-Fong Lee, Ahmed Atef Ahmed Ali, Tsung-Chih Chen, Hsu-Shan Huang, Kuo-Hsing Ma
The small-molecule naphtha [2,3-f]quinoxaline-7,12-dione (NSC745887) can effectively inhibit the proliferation of various cancers by trapping DNA-topoisomerase cleavage. The aim of this study was to elucidate cellular responses of NSC745887 in human glioblastoma multiforme (GBM, U118MG and U87MG cells) and investigate the underlying molecular mechanisms. NSC745887 reduced the cell survival rate and increased the sub-G1 population in dose- and time-dependent manners in GBM cells. Moreover, NSC745887 increased expression of γH2AX and caused DNA fragmentation leading to DNA damage...
February 23, 2018: Oncotarget
Hui Di, Xinting Zhang, Yi Guo, Yanfang Shi, Chuan Fang, Yu Yuan, Jiwei Wang, Chao Shang, Wenzhe Guo, Chunhui Li
Glioblastoma multiforme (GBM) is a prevalent and aggressive disease, and the development of a novel therapy to better treat advanced GBM is urgently required. Lactate dehydrogenase A (LDHA), which functions as a key enzyme in transforming pyruvate into lactate, has attracted more attention in recent years due to its critical role in various types of advanced cancer. Previous data derived from the Oncomine database have shown that the expression of LDHA is higher in GBM tissues than that in corresponding normal control tissues...
April 2018: Oncology Letters
Cindy R Timme, Barbara H Rath, John W O'Neill, Kevin Camphausen, Philip J Tofilon
Radiotherapy is a primary treatment modality for glioblastomas (GBMs). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSBs), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation...
March 16, 2018: Molecular Cancer Therapeutics
Amelia Weber Hall, Anna M Battenhouse, Haridha Shivram, Adam R Morris, Matthew C Cowperthwaite, Max Shpak, Vishwanath R Iyer
Glioblastoma multiforme (GBM) can be clustered by gene expression into four main subtypes associated with prognosis and survival, but enhancers and other gene regulatory elements have not yet been identified in primary tumors. Here, we profiled six histone modifications and CTCF binding as well as gene expression in primary gliomas, and identified chromatin states that define distinct regulatory elements across the tumor genome. Enhancers in mesenchymal and classical tumor subtypes drove gene expression associated with cell migration and invasion, while enhancers in proneural tumors controlled genes associated with a less aggressive phenotype in GBM...
March 16, 2018: Cancer Research
Yu-Shui Ma, Zhi-Jun Wu, Rui-Zhen Bai, Hua Dong, Bing-Xue Xie, Xiao-Hong Wu, Xiao-Sheng Hang, Ai-Ning Liu, Xiao-Hui Jiang, Gao-Ren Wang, Jun-Jian Jiang, Wen-Huan Xu, Xiao-Ping Chen, Guang-Hong Tan, Da Fu, Ji-Bin Liu, Quan Liu
Metastatic invasion is the primary cause of treatment failure for GBM. EMT is one of the most important events in the invasion of GBM; therefore, understanding the molecular mechanisms of EMT is crucial for the treatment of GBM. In this study, high expression of DRR1 was identified to correlate with a shorter median overall and relapse-free survival. Loss-of-function assays using shDRR1 weakened the invasive potential of the GBM cell lines through regulation of EMT-markers. The expressions of p-AKT were significantly decreased after DRR-depletion in SHG44 and U373 cells...
March 13, 2018: Cancer Letters
Zachary J Reitman, Frank Winkler, Andrew E H Elia
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis...
February 2018: Seminars in Neurology
Kyle L Brown, Billy G Hudson, Paul A Voziyan
PURPOSE OF REVIEW: The purpose of this review is to highlight recent advances in understanding the molecular assembly of basement membranes, as exemplified by the glomerular basement membrane (GBM) of the kidney filtration apparatus. In particular, an essential role of halogens in the basement membrane formation has been discovered. RECENT FINDINGS: Extracellular chloride triggers a molecular switch within non collagenous domains of collagen IV that induces protomer oligomerization and scaffold assembly outside the cell...
March 15, 2018: Current Opinion in Nephrology and Hypertension
IlKyoo Koh, Junghwa Cha, Junseong Park, Junjeong Choi, Seok-Gu Kang, Pilnam Kim
Glioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion...
March 15, 2018: Scientific Reports
Jennifer Power, Gosia Mikołajczak, Adam Bourne, Graham Brown, William Leonard, Anthony Lyons, Gary W Dowsett, Jayne Lucke
Background: This paper explores associations between use of party-and-play drugs, including crystal methamphetamine, and wellbeing among HIV positive gay and bisexual men (GBM) in Australia. This study considers whether use of drugs in a social or sex-based setting facilitates access to social and support networks, which may in turn support wellbeing. Methods: A cross-sectional survey of Australian people living with HIV (PLHIV) was conducted. There were 714 participants (79.7%) who identified as GBM. Differences between party-and-play drug users and non-users were examined using bivariate and multinomial logistic regressions...
March 16, 2018: Sexual Health
Carmen J Zamora-Sánchez, Aylin Del Moral-Morales, Ana M Hernández-Vega, Valeria Hansberg-Pastor, Ivan Salido-Guadarrama, Mauricio Rodríguez-Dorantes, Ignacio Camacho-Arroyo
Glioblastomas (GBM) are the most frequent and aggressive brain tumors. In these malignancies, progesterone (P4) promotes proliferation, migration, and invasion. The P4 metabolite allopregnanolone (3α-THP) similarly promotes cell proliferation in the U87 human GBM cell line. Here, we evaluated global changes in gene expression of U87 cells treated with 3α-THP, P4, and the 5α-reductase inhibitor, finasteride (F). 3α-THP modified the expression of 137 genes, while F changed 90. Besides, both steroids regulated the expression of 69 genes...
March 15, 2018: International Journal of Molecular Sciences
Bárbara da Silva, Ryan K Mathew, Euan S Polson, Jennifer Williams, Heiko Wurdak
Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs)...
March 1, 2018: SLAS Discovery
Manijeh Beigi, Kevan Ghasemi, Parvin Mirzaghavami, Mohammadreza Khanmohammadi, Hamidreza SalighehRad
The main aim of this study was to propose a new statistical method for evaluation of spatial malignancy distribution within Magnetic Resonance Spectroscopy (MRS) grid in Glioblastoma Multiforme patients. Voxels with different malignancy probabilities were presented as a novel MRS-based Malignancy Probability Map (MPM). For this purpose, a predictive probability-based clustering approach was developed, including the two following steps: (1) Gaussian Mixture Model, (2) Quadratic Discriminate Analysis coupled with Genetic Algorithm...
March 14, 2018: Journal of Neuro-oncology
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