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https://www.readbyqxmd.com/read/29786075/tp53-gain-of-function-mutation-promotes-inflammation-in-glioblastoma
#1
Seok Won Ham, Hee-Young Jeon, Xiong Jin, Eun-Jung Kim, Jun-Kyum Kim, Yong Jae Shin, Yeri Lee, Se Hoon Kim, Seon Yong Lee, Sunyoung Seo, Min Gi Park, Hye-Mi Kim, Do-Hyun Nam, Hyunggee Kim
Glioblastoma (GBM), the most severe and common brain tumor in adults, is characterized by multiple somatic mutations and aberrant activation of inflammatory responses. Immune cell infiltration and subsequent inflammation cause tumor growth and resistance to therapy. Somatic loss-of-function mutations in the gene encoding tumor suppressor protein p53 (TP53) are frequently observed in various cancers. However, numerous studies suggest that TP53 regulates malignant phenotypes by gain-of-function (GOF) mutations...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785566/delineating-a-new-feature-of-constitutional-mismatch-repair-deficiency-cmmrd-syndrome-breast-cancer
#2
Lisa Bush, Melyssa Aronson, Uri Tabori, Brittany B Campbell, Raymond B Bedgood, Kory Jasperson
Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive hereditary cancer condition, characterized by an exceptionally high risk of cancer, a propensity for childhood malignancies, and cutaneous features reminiscent of neurofibromatosis type 1 (NF1). We report on two sisters originally suspected of having CMMRD syndrome due to their history of colonic polyps and NF1 associated skin findings, both were subsequently found to have biallelic MSH6 mutations. After years of CMMRD syndrome follow-up, the proband was diagnosed with breast cancer at age 29, while her sister was diagnosed with a glioblastoma at age 27...
May 21, 2018: Familial Cancer
https://www.readbyqxmd.com/read/29784746/role-of-molecular-pathology-in-the-treatment-of-anaplastic-gliomas-and-glioblastomas
#3
Matthias Holdhoff
The 2016 WHO Classification of Tumors of the Central Nervous System integrated molecular biomarkers into the classifications of malignant gliomas. Several markers now play a key role in our understanding of these tumors and are integral for clinical decision-making; these include codeletion of 1p and 19q and IDH1 and IDH2 mutations. The presentation by Matthias Holdhoff, MD, PhD, at the NCCN 23rd Annual Conference discussed the current understanding of anaplastic gliomas (WHO grade III) in the context of the new classification and its implications on clinical practice...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29784452/regulation-of-the-oxidative-balance-with-coenzyme-q10-sensitizes-human-glioblastoma-cells-to-radiation-and-temozolomide
#4
Javier Frontiñán-Rubio, Raquel María Santiago-Mora, Consuelo María Nieva-Velasco, Gustavo Ferrín, Alicia Martínez-González, María Victoria Gómez, María Moreno, Julia Ariza, Eva Lozano, Jacinto Arjona-Gutiérrez, Antonio Gil-Agudo, Manuel De la Mata, Milica Pesic, Juan Ramón Peinado, José M Villalba, Luis Pérez-Romasanta, Víctor M Pérez-García, Francisco J Alcaín, Mario Durán-Prado
OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2 - ) and H2 O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time...
May 18, 2018: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29784026/effects-of-ionizing-radiation-on-the-viability-and-proliferative-behavior-of-the-human-glioblastoma-t98g-cell-line
#5
Hossam Murad, Yaman Alghamian, Abdulmunim Aljapawe, Ammar Madania
OBJECTIVE: Radiotherapy is the traditional therapy for glioma patients. Glioma has poor response to ionizing radiation (IR). Studying radiation-induced cell death can help in understanding the cellular mechanisms underlying its radioresistance. T98G cell line was irradiated with Co60 source by 2 or 10 Gy. MTT assay was used to calculate the surviving fraction. Cell viability, cell cycle distribution and apoptosis assays were conducted by flow cytometry for irradiated and control cells for the 10 Gy dose...
May 21, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29783757/a-repurposed-drug-for-brain-cancer-enhanced-atovaquone-amorphous-solid-dispersion-by-combining-a-spontaneously-emulsifying-component-with-a-polymer-carrier
#6
Hiroyuki Takabe, Zachary N Warnken, Yajie Zhang, Daniel A Davis, Hugh D C Smyth, John G Kuhn, Steve Weitman, Robert O Williams Iii
Glioblastoma multiforme (GBM) is the most common and lethal central nervous system tumor. Recently, atovaquone has shown inhibition of signal transducer and activator transcription 3, a promising target for GBM therapy. However, it is currently unable to achieve therapeutic drug concentrations in the brain with the currently reported and marketed formulations. The present study sought to explore the efficacy of atovaquone against GBM as well as develop a formulation of atovaquone that would improve oral bioavailability, resulting in higher amounts of drug delivered to the brain...
May 19, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29782850/histone-deacetylase-1-promotes-glioblastoma-cell-proliferation-and-invasion-via-activation-of-pi3k-akt-and-mek-erk-signaling-pathways
#7
Shun Li, Xiangrong Chen, Lifang Mao, Kashif Rafiq Zahid, Jun Wen, Liu Zhang, Maoying Zhang, Junwei Duan, Jie Duan, Xiaohong Yin, Yuanchuan Wang, Long Zhao, Xiaoping Tang, Xiangyu Wang, Guozheng Xu
Histone deacetylase 1 (HDAC1) plays a crucial role in cancer progression and development. This enzyme has been confirmed to be a key regulator of tumor biology functions, such as tumor cell proliferation, migration and invasion. However, HDAC1 expression in glioma remains controversial, and its specific function and molecular mechanism in glioblastoma is poorly understood. In this study, our findings demonstrated that protein and mRNA levels of HDAC1 were increased in glioma cell lines and glioma tissues compared to normal glial cell lines and non-neoplastic brain tissues, respectively...
May 18, 2018: Brain Research
https://www.readbyqxmd.com/read/29782366/single-agent-bevacizumab-in-recurrent-glioblastoma-after-second-line-chemotherapy-with-fotemustine-the-experience-of-the-italian-association-of-neuro-oncology
#8
Francesco Pasqualetti, Andrea Pace, Alessandra Gonnelli, Veronica Villani, Martina Cantarella, Durim Delishaj, Caterina Vivaldi, Alessandro Molinari, Sabrina Montrone, Alessia Pellerino, Federica Franchino, Davide Baldaccini, Giuseppe Lombardi, Ivan Lolli, Francesca Catania, Elena Bazzoli, Riccardo Morganti, Alessandra Fabi, Vittorina Zagonel, Guido Bocci, Maria Grazia Fabrini, Roberta Rudà, Riccardo Soffietti, Fabiola Paiar
OBJECTIVES: Bevacizumab is an anti-vascular endothelial growth factor antibody used in the treatment of recurrent glioblastoma (GBM). Despite the large number of studies carried out in patients with recurrent GBM, little is known about the administration of this angiogenesis inhibitor after the failure of the second-line chemotherapy. MATERIALS AND METHODS: In this retrospective multicenter study, on behalf of the Italian Association of Neuro-Oncology, we reported the results obtained in 51 patients with recurrent GBM treated with single-agent bevacizumab after the failure of second-line chemotherapy with fotemustine...
May 18, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29781781/gene-expression-microarray-analysis-reveals-prognostic-markers-of-survival-in-high-grade-astrocytomas
#9
Jun Yang, Ziming Hou, Changjiang Wang, Hao Wang, Hongbing Zhang
OBJECTIVE: High grade astrocytoma (HGA) as an aggressive brain tumor, is always correlated with poor prognosis. In this paper, we aimed to explore the genetic prognostic biomarkers for HGA. METHODS: The genome-wide expression profile of 26 brain tumor samples obtained from 26 patients with HGA was downloaded from Gene Expression Omnibus. The risk genes for prognosis of HGA were identified and verified by the data in TCGA database. Protein-protein interaction (PPI) network of risk factor genes was constructed and significant module was screened...
May 21, 2018: Neurological Research
https://www.readbyqxmd.com/read/29780878/microfluidics-in-malignant-glioma-research-and-precision-medicine
#10
Meghan Logun, Wujun Zhao, Leidong Mao, Lohitash Karumbaiah
Glioblastoma multiforme (GBM) is an aggressive form of brain cancer that has no effective treatments and a prognosis of only 12-15 months. Microfluidic technologies deliver microscale control of fluids and cells, and have aided cancer therapy as point-of-care devices for the diagnosis of breast and prostate cancers. However, a few microfluidic devices are developed to study malignant glioma. The ability of these platforms to accurately replicate the complex microenvironmental and extracellular conditions prevailing in the brain and facilitate the measurement of biological phenomena with high resolution and in a high-throughput manner could prove useful for studying glioma progression...
May 2018: Advanced Biosystems
https://www.readbyqxmd.com/read/29780826/silibinin-induced-human-glioblastoma-cell-apoptosis-concomitant-with-autophagy-through-simultaneous-inhibition-of-mtor-and-yap
#11
Zhuan-Li Bai, Vincent Tay, Shu-Zhong Guo, Juan Ren, Mao-Guo Shu
Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum . Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29780818/basic-and-translational-advances-in-glioblastoma
#12
EDITORIAL
Sara G M Piccirillo, Marta M Alonso, Francesco Pasqualetti
No abstract text is available yet for this article.
2018: BioMed Research International
https://www.readbyqxmd.com/read/29780166/nudt21-negatively-regulates-psmb2-and-cxxc5-by-alternative-polyadenylation-and-contributes-to-hepatocellular-carcinoma-suppression
#13
Sheng Tan, Hua Li, Weijie Zhang, Yunying Shao, Yuan Liu, Haiyang Guan, Jun Wu, Yani Kang, Junsong Zhao, Qing Yu, Yunzhao Gu, Keshuo Ding, Min Zhang, Wenchang Qian, Yong Zhu, Huayong Cai, Changyu Chen, Peter E Lobie, Xiaodong Zhao, Jielin Sun, Tao Zhu
Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and involved in many diseases, including cancer. CFIm25, a subunit of the cleavage factor I encoded by NUDT21, is required for 3'RNA cleavage and polyadenylation. Although it has been recently reported to be involved in glioblastoma tumor suppression, its roles and the underlying functional mechanism remain unclear in other types of cancer. In this study, we characterized NUDT21 in hepatocellular carcinoma (HCC). Reduced expression of NUDT21 was observed in HCC tissue compared to adjacent non-tumorous compartment...
May 21, 2018: Oncogene
https://www.readbyqxmd.com/read/29779087/down-regulation-of-mdr1-by-ad-dkk3-via-akt-nf%C3%AE%C2%BAb-pathways-augments-the-anti-tumor-effect-of-temozolomide-in-glioblastoma-cells-and-a-murine-xenograft-model
#14
Toshitaka Fujihara, Yoshifumi Mizobuchi, Kohei Nakajima, Teruyoshi Kageji, Kazuhito Matsuzaki, Keiko T Kitazato, Ryotaro Otsuka, Keijiro Hara, Hideo Mure, Toshiyuki Okazaki, Kazuyuki Kuwayama, Shinji Nagahiro, Yasushi Takagi
BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant of brain tumors. Acquired drug resistance is a major obstacle for successful treatment. Earlier studies reported that expression of the multiple drug resistance gene (MDR1) is regulated by YB-1 or NFκB via the JNK/c-Jun or Akt pathway. Over-expression of the Dickkopf (DKK) family member DKK3 by an adenovirus vector carrying DKK3 (Ad-DKK3) exerted anti-tumor effects and led to the activation of the JNK/c-Jun pathway. We investigated whether Ad-DKK3 augments the anti-tumor effect of temozolomide (TMZ) via the regulation of MDR1...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29779086/retrospective-study-of-nivolumab-for-patients-with-recurrent-high-grade-gliomas
#15
Megan Mantica, Ashley Pritchard, Frank Lieberman, Jan Drappatz
INTRODUCTION: Patients with recurrent high-grade gliomas (HGG) have limited treatment options. HGG utilize the PD-1 pathway to evade immune responses. Checkpoint inhibitors have demonstrated safety and clinical activity in patients with recurrent glioblastoma. We explored the efficacy of nivolumab in recurrent HGG with a primary objective of progression free survival (PFS) and overall survival (OS). METHODS: We retrospectively analyzed HGG patients treated with nivolumab in our institution...
May 19, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29778285/subcutaneous-tissue-metastasis-from-glioblastoma-multiforme-a-case-report-and-review-of-the-literature
#16
Natalia Frade Porto, Juan Delgado Fernández, María de Los Ángeles García Pallero, Juan Ramón Penanes Cuesta, Paloma Pulido Rivas, Ricardo Gil Simoes
Glioblastoma multiforme is the most common primary brain tumor, despite an aggressive clinical course, less than 2% of patients develop extraneural metastasis. We present a 72-year-old male diagnosed with a right temporal glioblastoma due to headache. He underwent total gross resection surgery and after that the patient was treated with adyuvant therapy. Five months after the patient returned with trigeminal neuralgia, and MRI showed an infratemporal cranial mass which infiltrates masticator space, the surrounding bone, the temporal muscle and superior cervical and parotid lymph nodes...
May 16, 2018: Neurocirugía
https://www.readbyqxmd.com/read/29777945/patterns-of-care-and-outcomes-of-chemoradiation-versus-radiation-alone-for-mgmt-promoter-unmethylated-glioblastoma
#17
Anna Lee, Nikita Malakhov, Niki Sheth, Arthur Wang, Peter Han, David Schreiber
OBJECTIVE: The recommended treatment for O6 -methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM) is radiation therapy with concurrent/adjuvant temozolomide (TMZ). However, it is well known that the clinical benefit from TMZ is lower in these patients. We sought to analyze patterns of care and outcomes of chemoradiation versus radiation alone in this cohort using a large, hospital database. PATIENTS AND METHODS: Patients diagnosed with MGMT promoter unmethylated GBM from 2010 to 2012 who received radiation (RT) or chemoradiation (CRT) were identified in the National Cancer Database...
May 16, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29777944/the-post-surgical-era-of-gbm-how-molecular-biology-has-impacted-on-our-clinical-management-a-review
#18
REVIEW
M Monticelli, P Zeppa, F Zenga, R Altieri, M Mammi, L Bertero, I Castellano, P Cassoni, A Melcarne, G La Rocca, G Sabatino, A Ducati, D Garbossa
Glioblastoma (GBM) is the most common glioma in adults, with incidence increasing by 3% per year. According to the World Health Organization Classification of Central Nervous System Tumors, GBM is considered a grade IV tumor due to its malignant behavior. The aim of this review is to summarize the main biological aspects of GBM. In particular, we focused our attention on those alterations which have been proven to have an impact on patients' outcome, mainly in terms of overall survival (OS), or on the tumor response to therapies...
May 16, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29777870/profiling-modifications-for-glioblastoma-proteome-using-ultra-tolerant-database-search-are-the-peptide-mass-shifts-biologically-relevant-or-chemically-induced
#19
Irina A Tarasova, Peter M Chumakov, Sergei A Moshkovskii, Mikhail V Gorshkov
Peptide mass shifts were profiled using ultra-tolerant database search strategy for shotgun proteomics data sets of human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The main objective of this profiling was revealing the cell response to IFN treatment at the level of protein modifications. To achieve this objective, statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples were analyzed. Detailed analysis of MS/MS spectra allowed further interpretation of the observed mass shifts and differentiation between post-translational and artifact modifications...
May 16, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29777576/glioblastoma-recurrence-correlates-with-nlgn3-levels
#20
Rui Liu, Xing-Ping Qin, Yang Zhuang, Ya Zhang, Hua-Bao Liao, Jun-Chun Tang, Meng-Xian Pan, Fei-Fei Zeng, Yang Lei, Rui-Xue Lei, Shu Wang, An-Chun Liu, Juan Chen, Zhi-Feng Zhang, Dan Zhao, Song-Lin Wu, Ren-Zhong Liu, Ze-Fen Wang, Qi Wan
Glioblastoma (GBM) is the most aggressive glioma in the brain. Recurrence of GBM is almost inevitable within a short term after tumor resection. In a retrospective study of 386 cases of GBM collected between 2013 and 2016, we found that recurrence of GBM mainly occurs in the deep brain regions, including the basal ganglia, thalamus, and corpus callosum. But the mechanism underlying this phenomenon is not clear. Previous studies suggest that neuroligin-3 (NLGN3) is necessary for GBM growth. Our results show that the levels of NLGN3 in the cortex are higher than those in the deep regions in a normal human brain, and similar patterns are also found in a normal mouse brain...
May 18, 2018: Cancer Medicine
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