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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
#1
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/29778770/age-related-prevalence-and-twelve-month-incidence-of-illicit-drug-use-in-a-cohort-of-australian-gay-and-bisexual-men-results-from-the-flux-study
#2
Fengyi Jin, Mohamed A Hammoud, Lisa Maher, Louisa Degenhardt, Adam Bourne, Toby Lea, Stefanie Vaccher, Jeffrey Grierson, Bridget Haire, Garrett P Prestage
BACKGROUND: We report prevalence and incidence of drug use initiation in Australian gay and bisexual men (GBM) participating in an online cohort study. METHODS: Between September 2014 and June 2015, 1,710 GBM were enrolled in the Following Lives Undergoing Change Study and followed-up six monthly. Participants were asked about measures of lifetime use at baseline and recent use (last six months) at all visits. Drug use initiation was defined as men who reported having never used a specific drug prior to baseline and reported recent use at follow-up...
May 12, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29777945/patterns-of-care-and-outcomes-of-chemoradiation-versus-radiation-alone-for-mgmt-promoter-unmethylated-glioblastoma
#3
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
#4
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/29777576/glioblastoma-recurrence-correlates-with-nlgn3-levels
#5
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
https://www.readbyqxmd.com/read/29777390/synergistic-effect-of-trail-and-irradiation-in-elimination-of-glioblastoma-stem-like-cells
#6
Junfeng Liu, Qinglei Gao, Tao Xie, Yu Liu, Longjun Luo, Cheng Xu, Lu Shen, Feng Wan, Ting Lei, Fei Ye
Glioblastoma multiforme (GBM) is the most common malignancy in central nervous system. A small subpopulation of GBM cells known as GBM stem-like cells (GSLCs) were supposed to be the most malignant cells among GBM cells as they are resistant to multiple therapies including radiotherapy. In this study, we set up two GSLCs cell lines from the two parental U87 and U251 glioma cell lines, and studied the expression of apoptosis-related genes alteration in GSLCs before and after irradiation. We found that one of the receptors of TNF-related apoptosis-inducing ligand (TRAIL), DR5, was dramatically up-regulated in GSLCs after irradiation (IR)...
May 18, 2018: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/29777137/enhanced-efficacy-of-combined-temozolomide-and-bromodomain-inhibitor-therapy-for-gliomas-using-targeted-nanoparticles
#7
Fred C Lam, Stephen W Morton, Jeffrey Wyckoff, Tu-Lan Vu Han, Mun Kyung Hwang, Amanda Maffa, Elena Balkanska-Sinclair, Michael B Yaffe, Scott R Floyd, Paula T Hammond
Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1...
May 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29775073/diffuse-gliomas-for-nonneuropathologists-the-new-integrated-molecular-diagnostics
#8
Sunhee C Lee
Diffuse gliomas comprise the bulk of "brain cancer" in adults. The recent update to the 4th edition of the World Health Organization's classification of tumors of the central nervous system reflects an unprecedented change in the landscape of the diagnosis and management of diffuse gliomas that will affect all those involved in the management and care of patients. Of the recently discovered gene alterations, mutations in the Krebs cycle enzymes isocitrate dehydrogenases (IDHs) 1 and 2 have fundamentally changed the way the gliomas are understood and classified...
May 18, 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29774876/-clinicopathological-features-for-epithelioid-glioblastoma-a-newly-defined-tumor-by-the-2016-world-health-organization-classification-of-tumors-of-the-central-nervous-system
#9
Juan Li, Xuebing Ling, Mingyao Lai, Qingjun Hu, Changguo Shan, Linbo Cai
To retrospectively summarize the clinicopathological features of epithelioid glioblastoma (Ep-GBM) and to explore new treatment for Ep-GBM.
 Methods: The clinical data of 13 patients with Ep-GBM, who were treated in our department from March 2016 to July 2017, were retrospectively analyzed. The clinicopathological features were summarized and the efficacy was evaluated.
 Results: The positive rate of BRAFV600E mutant and INI-1 was 76.9% (10/13) and 80% (8/10), respectively, while the median Ki-67 index was 30%...
April 28, 2018: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29774498/microrna-1231-exerts-a-tumor-suppressor-role-through-regulating-the-egfr-pi3k-akt-axis-in-glioma
#10
Jiale Zhang, Jie Zhang, Wenjin Qiu, Jian Zhang, Yangyang Li, Enjun Kong, Ailin Lu, Jia Xu, Xiaoming Lu
PURPOSE: MicroRNAs (miRNAs) have been shown to be involved in the initiation and progression of glioma. However, the underlying molecular mechanisms are still unclear. METHODS: We performed microarray analysis to evaluate miRNA expression levels in 158 glioma tissue samples, and examined miR-1231 levels in glioma samples and healthy brain tissues using qRT-PCR. In vitro analyses were performed using miR-1231 mimics, inhibitors, and siRNA targeting EGFR. We used flow cytometry, CCK-8 assays, and colony formation assays to examine glioma proliferation and cell cycle analysis...
May 17, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29774180/survival-prediction-based-on-qualitative-mri-diffusion-signature-in-patients-with-recurrent-high-grade-glioma-treated-with-bevacizumab
#11
Pradeep Goyal, Mary Tenenbaum, Sonali Gupta, Puneet S Kochar, Alok A Bhatt, Manisha Mangla, Yogesh Kumar, Rajiv Mangla
Background: Bevacizumab was approved by the FDA for the treatment of recurrent or progressive glioblastoma (GBM). Imaging responses are typically assessed by gadolinium-enhanced MRI. We sought to determine the significance of qualitative diffusion signature (manifest as variable degree of dark signal) on ADC maps in recurrent gliomas after treatment with bevacizumab. Methods: We performed an institutional review board (IRB) approved retrospective study on patients who underwent MRI of the brain after 8 weeks of receiving bevacizumab for recurrent glioma...
April 2018: Quantitative Imaging in Medicine and Surgery
https://www.readbyqxmd.com/read/29774132/natural-products-a-hope-for-glioblastoma-patients
#12
REVIEW
Raghupathy Vengoji, Muzafar A Macha, Surinder K Batra, Nicole A Shonka
Glioblastoma (GBM) is one of the most aggressive malignant tumors with an overall dismal survival averaging one year despite multimodality therapeutic interventions including surgery, radiotherapy and concomitant and adjuvant chemotherapy. Few drugs are FDA approved for GBM, and the addition of temozolomide (TMZ) to standard therapy increases the median survival by only 2.5 months. Targeted therapy appeared promising in in vitro monolayer cultures, but disappointed in preclinical and clinical trials, partly due to the poor penetration of drugs through the blood brain barrier (BBB)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774125/the-critical-role-that-stat3-plays-in-glioma-initiating-cells-stat3-addiction-in-glioma
#13
Debolina Ganguly, Meiyun Fan, Chuan He Yang, Blazej Zbytek, David Finkelstein, Martine F Roussel, Lawrence M Pfeffer
Glioma-Initiating Cells (GICs) are thought to be responsible for tumor initiation, progression and recurrence in glioblastoma (GBM). In previous studies, we reported the constitutive phosphorylation of the STAT3 transcription factor in GICs derived from GBM patient-derived xenografts, and that STAT3 played a critical role in GBM tumorigenesis. In this study, we show that CRISPR/Cas9-mediated deletion of STAT3 in an established GBM cell line markedly inhibited tumorigenesis by intracranial injection but had little effect on cell proliferation in vitro ...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773903/circadian-regulator-nr1d2-regulates-glioblastoma-cell-proliferation-and-motility
#14
Min Yu, Wenjing Li, Qianqian Wang, Yan Wang, Fei Lu
Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29771386/immunotherapy-in-cns-cancers-the-role-of-immune-cell-trafficking
#15
Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden...
May 15, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29770193/hyperbaric-oxygen-therapy-as-adjunctive-strategy-in-treatment-of-glioblastoma-multiforme
#16
REVIEW
Lei Huang, Warren Boling, John H Zhang
Glioblastoma multiforme (GBM) is the most common type of malignant intracranial tumor in adults. Tumor tissue hypoxia, high mitotic rate, and rapid tumor spread account for its poor prognosis. Hyperbaric oxygen therapy (HBOT) may improve the sensitivity of radio-chemotherapy by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. This review summarizes the research of HBOT applications within the context of experimental and clinical GBM. Limited clinical trials and preclinical studies suggest that radiotherapy immediately after HBOT enhances the effects of radiotherapy in some aspects...
January 2018: Medical Gas Research
https://www.readbyqxmd.com/read/29770114/extracts-of-artocarpus-communis-induce-mitochondria-associated-apoptosis-via-pro-oxidative-activity-in-human-glioblastoma-cells
#17
Chiang-Wen Lee, Lee-Fen Hsu, Ming-Hsueh Lee, I-Ta Lee, Ju-Fang Liu, Yao-Chang Chiang, Ming-Horng Tsai
Glioblastoma multiforme (GBM) is an extremely aggressive and devastating malignant tumor in the central nervous system. Its incidence is increasing and the prognosis is poor. Artocarpin is a natural prenylated flavonoid with various anti-inflammatory and anti-tumor properties. Studies have shown that artocarpin is associated with cell death of primary glioblastoma cells. However, the in vivo effects and the cellular and molecular mechanisms modulating the anticancer activities of artocarpin remain unknown. In this study, we demonstrated that treating the glioblastoma cell lines U87 and U118 cells with artocarpin induced apoptosis...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29769617/a-new-method-of-identifying-glioblastoma-subtypes-and-creation-of-corresponding-animal-models
#18
Xia Zhou, Gonghua Li, Sanqi An, Wen-Xing Li, Huihui Yang, Yicheng Guo, Zhi Dai, Shaoxing Dai, Junjuan Zheng, Jingfei Huang, Antonio Iavarone, Xudong Zhao
Glioblastoma (GBM) accounts for up to 50% of brain parenchymal tumors. It is the most malignant type of brain cancer with very poor survival and limited remedies. Cancer subtyping is important for cancer research and therapy. Here, we report a new subtyping method for GBM based on the genetic alterations of CDKN2A and TP53 genes. CDKN2A and TP53 are the most frequently mutated genes with mutation rates of 60 and 30%, respectively. We found that patients with deletion of CDKN2A possess worse survival than those with TP53 mutation...
May 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29769450/heat-shock-protein-peptide-complex-96-vaccination-for-newly-diagnosed-glioblastoma-a-phase-i-single-arm-trial
#19
Nan Ji, Yang Zhang, Yunpeng Liu, Jian Xie, Yi Wang, Shuyu Hao, Zhixian Gao
BACKGROUND: Heat shock protein peptide complex-96 (HSPPC-96) triggers adaptive and innate antitumor immune responses. The safety and efficacy of HSPPC-96 vaccination was examined in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: In this open-label, single-arm, phase I study, adult patients were vaccinated with HSPPC-96 in combination with the standard treatment for newly diagnosed GBM after surgical resection. Primary endpoints were frequency of adverse events and progression-free survival (PFS) at 6 months...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29769444/glioblastoma-targeted-cd4-car-t-cells-mediate-superior-antitumor-activity
#20
Dongrui Wang, Brenda Aguilar, Renate Starr, Darya Alizadeh, Alfonso Brito, Aniee Sarkissian, Julie R Ostberg, Stephen J Forman, Christine E Brown
Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2)...
May 17, 2018: JCI Insight
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