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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/27921110/multifunctional-pei-entrapped-gold-nanoparticles-enable-efficient-delivery-of-therapeutic-sirna-into-glioblastoma-cells
#2
Lingdan Kong, Jieru Qiu, Wenjie Sun, Jia Yang, Mingwu Shen, Lu Wang, Xiangyang Shi
RNA interference (RNAi) has been considered as a promising strategy for effective treatment of cancer. However, the easy degradation of small interfering RNA (siRNA) limits its extensive applications in gene therapy. For safe and effective delivery of siRNA, a novel vector system possessing excellent biocompatibility, highly efficient transfection efficiency and specific targeting properties has to be considered. In this study, we report the use of polyethyleneimine (PEI)-entrapped gold nanoparticles (Au PENPs) modified with an arginine-glycine-aspartic (Arg-Gly-Asp, RGD) peptide via a poly(ethylene glycol) (PEG) spacer as a vector for Bcl-2 (B-cell lymphoma-2) siRNA delivery to glioblastoma cells...
December 6, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27920947/the-daniel-k-inouye-college-of-pharmacy-scripts-poha-berry-physalis-peruviana-with-potential-anti-inflammatory-and-cancer-prevention-activities
#3
Leng Chee Chang, Mayuramas Sang-Ngern, John M Pezzuto, Carolyn Ma
The Daniel K. Inouye College of Pharmacy, during a historic event in Spring 2016, graduated the first two students in the Pacific region to earn a PhD in pharmaceutical sciences at the University of Hawai'i at Hilo. The college offers PhD programs in these five disciplines: Cancer Biology, Medicinal Chemistry, Pharmaceutics, Pharmacognosy, and Pharmacology. One of the Pharmacognosy dissertations focused on plant-derived natural products with potential anti-inflammatory and cancer chemopreventive activities...
November 2016: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/27920004/down-regulation-of-microrna-126-in-glioblastoma-and-its-correlation-with-patient-prognosis-a-pilot-study
#4
In Bo Han, Minsoo Kim, Soo Hong Lee, Jin Kwon Kim, Se Hoon Kim, Jong Hee Chang, Yang D Teng
Glioblastoma is the most common primary malignant tumor of the adult human brain. Although microRNA-126 (miR-126) has been reported to exhibit expression abnormalities in various types of cancer, to date very few studies have examined changes in miR-126 level in glioblastoma. In this pilot study, we investigated the changes in miR-126 expression in newly-dissected primary glioblastoma to explore possible roles of miR-126 in patient prognosis. Total RNA was extracted from tumoral and adjacent non-cancerous tissues from 14 patients' paired frozen specimens...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919957/simultaneous-administration-of-statins-and-pioglitazone-limits-tumor-growth-in-a-rat-model-of-malignant-glioma
#5
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27919613/cellular-uptake-of-glucoheptoamidated-poly-amidoamine-pamam-g3-dendrimer-with-amide-conjugated-biotin-a-potential-carrier-of-anticancer-drugs
#6
Łukasz Uram, Magdalena Szuster, Aleksandra Filipowicz, Magdalena Zaręba, Elżbieta Wałajtys-Rode, Stanisław Wołowiec
In search for soluble derivatives of PAMAM dendrimers as potential carriers for hydrophobic drugs, the conjugates of PAMAM G3 with biotin, further converted into glycodendrimer with d-glucoheptono-1,4-lactone, were prepared. Polyamidoamine dendrimer (PAMAM) of third generation, G3 was functionalized with four biotin equivalents covalently attached to terminal amine nitrogens via amide bond G3(4B). The remaining 28 amine groups were blocked by glucoheptoamide substituents (gh) to give G3(4B28gh) or with one fluorescein equivalent (attached by reaction of G3(4B) with fluorescein isothiocyanate, FITC) via thiourea bond as FITC followed by exhaustive glucoheptoamidation to get G3(4B27gh1F)...
November 25, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27918718/randomized-double-blind-placebo-controlled-multicenter-phase-ii-study-of-onartuzumab-plus-bevacizumab-versus-placebo-plus-bevacizumab-in-patients-with-recurrent-glioblastoma-efficacy-safety-and-hepatocyte-growth-factor-and-o-6-methylguanine-dna-methyltransferase
#7
Timothy Cloughesy, Gaetano Finocchiaro, Cristóbal Belda-Iniesta, Lawrence Recht, Alba A Brandes, Estela Pineda, Tom Mikkelsen, Olivier L Chinot, Carmen Balana, David R Macdonald, Manfred Westphal, Kirsten Hopkins, Michael Weller, Carlos Bais, Thomas Sandmann, Jean-Marie Bruey, Hartmut Koeppen, Bo Liu, Wendy Verret, See-Chun Phan, David S Shames
Purpose Bevacizumab regimens are approved for the treatment of recurrent glioblastoma in many countries. Aberrant mesenchymal-epithelial transition factor (MET) expression has been reported in glioblastoma and may contribute to bevacizumab resistance. The phase II study GO27819 investigated the monovalent MET inhibitor onartuzumab plus bevacizumab (Ona + Bev) versus placebo plus bevacizumab (Pla + Bev) in recurrent glioblastoma. Methods At first recurrence after chemoradiation, bevacizumab-naïve patients with glioblastoma were randomly assigned 1:1 to receive Ona (15 mg/kg, once every 3 weeks) + Bev (15 mg/kg, once every 3 weeks) or Pla + Bev until disease progression...
December 5, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27918194/first-report-of-tumor-treating-fields-use-in-combination-with-bevacizumab-in-a-pediatric-patient-a-case-report
#8
Daniel O'Connell, Violet Shen, William Loudon, Daniela A Bota
We report the first case of a pediatric patient with glioblastoma (GBM; WHO grade IV astrocytoma) successfully treated with tumor treating fields (TTF). The patient was diagnosed with GBM when 13 years of age and progressed through surgical resection, radiotherapy and chemotherapy. Discrete tumor growth visualized on MRI with stable neurological examination was monitored for 6 months with subsequent stable disease observed radiographically and clinically for 7 months while adherent to Optune(®) (TTF). TTF thereby played a role in forestalling recurrent GBM growth in this young woman for 7 months without significant adverse effects...
December 5, 2016: CNS Oncology
https://www.readbyqxmd.com/read/27917302/characterization-of-the-blood-brain-barrier-in-pediatric-central-nervous-system-neoplasms
#9
Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, John D Heiss
OBJECTIVE: The normal blood-brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors. MATERIALS AND METHODS: Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4)...
2016: Journal of Interdisciplinary Histopathology
https://www.readbyqxmd.com/read/27915974/targeting-autophagy-in-glioblastoma
#10
Janis Noonan, Jennifer Zarrer, Brona M Murphy
The role of autophagy in cancer cell survival and cell death has received much attention in recent years; however, scientists are still trying to unravel the complex relationship that exists between autophagy as a tumor suppressor mechanism and as a promoter of tumor progression. In glioblastoma (GBM), the most fatal tumor of the central nervous system, mounting evidence suggests that autophagy processes are tightly intertwined with GBM tumorigenesis and the development of different molecular subtypes. This has led to exciting prospects that autophagy-targeted therapies may improve the efficacy of conventional therapies as well as therapies targeted at specific genetic alterations in individual GBM patients...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27913976/follistatin-like-protein-1-suppressed-pro-inflammatory-cytokines-expression-during-neuroinflammation-induced-by-lipopolysaccharide
#11
Kai-Yuan Cheng, Yi Liu, Ying-Guang Han, Jing-Kun Li, Jia-Lin Jia, Bin Chen, Zhi-Xiao Yao, Lin Nie, Lei Cheng
Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment...
December 2, 2016: Journal of Molecular Histology
https://www.readbyqxmd.com/read/27913393/epigenetically-activated-wnt5a-promotes-glioblastoma-progression
#12
(no author information available yet)
WNT5A signaling drives an endothelial cell transcriptional program in GBM stem cells.
December 2, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27911816/rapid-emergence-and-mechanisms-of-resistance-by-u87-glioblastoma-cells-to-doxorubicin-in-an-in-vitro-tumor-microfluidic-ecology
#13
Jeonghun Han, Yukyung Jun, So Hyun Kim, Hong-Hoa Hoang, Yeonjoo Jung, Suyeon Kim, Jaesang Kim, Robert H Austin, Sanghyuk Lee, Sungsu Park
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911279/microrna-101-inhibits-proliferation-migration-and-invasion-of-human-glioblastoma-by-targeting-sox9
#14
Nan Liu, Lei Zhang, Zhen Wang, Yingduan Cheng, Pengxing Zhang, Xin Wang, Weihong Wen, Hongwei Yang, Hui Liu, Weilin Jin, Yongsheng Zhang, Yanyang Tu
Glioblastoma multiforme (GBM) is the most common primary malignant tumors originating in the brain parenchyma. At present, GBM patients have a poor prognosis despite the continuous progress in therapeutic technologies including surgery, radiotherapy, photodynamic therapy, and chemotherapy. Recent studies revealed that miR-101 was remarkably down-regulated in kinds of human cancers and was associated with aggressive tumor cell proliferation and stem cell self-renewal. Data also showed that miR-101 was down-regulated in primary glioma samples and cell lines, but the underlying molecular mechanism of the deregulation of miR-101 in glioma remained largely unknown...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910945/thyroid-transcription-factor-1-distinguishes-subependymal-giant-cell-astrocytoma-from-its-mimics-and-supports-its-cell-origin-from-the-progenitor-cells-in-the-medial-ganglionic-eminence
#15
Jen-Fan Hang, Chih-Yi Hsu, Shih-Chieh Lin, Chih-Chun Wu, Han-Jui Lee, Donald Ming-Tak Ho
Subependymal giant cell astrocytoma is a benign brain tumor mostly associated with tuberous sclerosis complex. However, it may be misinterpreted as other high-grade brain tumors due to the presence of large tumor cells with conspicuous pleomorphism and occasional atypical features, such as tumor necrosis and endothelial proliferation. In this study, we first investigated thyroid transcription factor-1 (TTF-1) expression in a large series of subependymal giant cell astrocytomas and other histologic and locational mimics to validate the diagnostic utility of this marker...
December 2, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27909720/tetrandrine-inhibits-glioma-stem-like-cells-by-repressing-%C3%AE-catenin-expression
#16
Yong Zhang, Yu-Lin Wen, Ji-Wei Ma, Jie-Cheng Ye, Xiao Wang, Jian-Xian Huang, Chao-Yue Meng, Xiao-Ze Xu, Shao-Xiang Wang, Xue-Yun Zhong
Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251...
November 23, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27909268/ten-year-review-of-survival-and-management-of-malignant-glioma-in-hong-kong
#17
D Tm Chan, S Yp Hsieh, C Ky Lau, M Km Kam, H Hf Loong, W K Tsang, D Mc Poon, W S Poon
INTRODUCTION: Surgical resection used to be the mainstay of treatment for glioma. In the last decade, however, opinion has changed about the goal of surgical resection in treating glioma. Ample evidence shows that maximum safe resection in glioblastoma improves survival. Neurosurgeons have therefore revised their objective of surgery from diagnostic biopsy or limited debulking to maximum safe resection. Given these changes in the management of glioma, we compared the survival of local Chinese patients with glioblastoma multiforme over a period of 10 years...
December 2, 2016: Hong Kong Medical Journal, Xianggang Yi Xue za Zhi
https://www.readbyqxmd.com/read/27909058/secreted-glioblastoma-nanovesicles-contain-intracellular-signaling-proteins-and-active-ras-incorporated-in-a-farnesylation-dependent-manner
#18
Natalie Luhtala, Aaron Aslanian, John R Yates, Tony Hunter
Glioblastomas (GBMs) are malignant brain tumors with a median survival of less than 18 months. Redundancy of signaling pathways represented within GBMs contributes to their therapeutic resistance. Exosomes are extracellular nanovesicles released from cells and present in human biofluids that represent a possible biomarker of tumor signaling state that could aid in personalized treatment. Herein, we demonstrate that mouse GBM cell-derived extracellular nanovesicles resembling exosomes from an H-RasV12 myr-Akt mouse model for GBM are enriched for intracellular signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and contain active Ras...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908799/isolation-of-novel-stilbenoids-from-the-roots-of-cyrtopodium-paniculatum-orchidaceae
#19
Florence Auberon, Opeyemi Joshua Olatunji, Diamondra Raminoson, Christian D Muller, Beatriz Soengas, Frédéric Bonté, Annelise Lobstein
Four new stilbenoids, named cyrtopodinone (1), cyrtopodinol (2), and coeludols A and B (3-4) were isolated from the roots of Cyrtopodium paniculatum, together with 21 known stilbenoids derivatives (5-25). Their structures were elucidated by comprehensive spectroscopic analysis including extensive 1D and 2D-NMR techniques. The cytotoxic activities of the isolated compounds were tested on human glioblastoma U-87MG cell line with fluorescence-based image cytometry. Only four compounds (18, 19, 22 and 25) displayed moderate cytotoxicity with IC50 values of 45...
November 28, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27908206/the-role-of-mesenchymal-stem-cells-in-oncology-and-regenerative-medicine
#20
Maliha Khan, Syeda Ezze Rukhshan Adil, Amanda L Olson
Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -β makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use...
December 2, 2016: Future Oncology
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