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https://www.readbyqxmd.com/read/28541444/blood-brain-barrier-pericyte-importance-in-malignant-gliomas-what-we-can-learn-from-stroke-and-alzheimer-s-disease
#1
Sadhana Jackson, Ayman ElAli, Daniela Virgintino, Mark R Gilbert
The pericyte, a constitutive component of the central nervous system, is a poorly understood cell type that envelops the endothelial cell with the intended purpose of regulating vascular flow and endothelial cell permeability. Previous studies of pericyte function have been limited to a small number of disease processes such as ischemic stroke and Alzheimer's disease. Recently, publications have postulated a link between glioma stem cell differentiation and pericyte function. These studies suggest that there may be an important interaction of pericytes with tumor cells and other components of the tumor microenvironment in malignant primary glial neoplasms, most notably glioblastoma...
May 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28536277/3d-mathematical-modeling-of-glioblastoma-suggests-that-transdifferentiated-vascular-endothelial-cells-mediate-resistance-to-current-standard-of-care-therapy
#2
Huaming Yan, Mónica Romero-López, Lesly I Benitez, Kaijun Di, Hermann B Frieboes, Christopher C W Hughes, Daniela A Bota, John S Lowengrub
Glioblastoma (GBM), the most aggressive brain tumor in human patients, is decidedly heterogeneous and highly vascularized. Glioma stem/initiating cells (GSC) are found to play a crucial role by increasing cancer aggressiveness and promoting resistance to therapy. Recently, crosstalk between GSC and vascular endothelial cells has been shown to significantly promote GSC self-renewal and tumor progression. Further, GSC also transdifferentiate into bona-fide vascular endothelial cells (GEC), which inherit mutations present in GSC and are resistant to traditional anti-angiogenic therapies...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28536141/melk-and-ezh2-cooperate-to-regulate-medulloblastoma-cancer-stem-like-cell-proliferation-and-differentiation
#3
Hailong Liu, Qianwen Sun, Youliang Sun, Junping Zhang, Hongyu Yuan, Shuhuan Pang, Xueling Qi, Haoran Wang, Mingshan Zhang, Honwei Zhang, Chunjiang Yu, Chunyu Gu
Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported that more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog (SHH)-subtype medulloblastoma...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28534509/a-novel-interaction-of-pak4-with-ppar%C3%AE-to-regulate-nox1-and-radiation-induced-epithelial-to-mesenchymal-transition-in-glioma
#4
D Kesanakurti, D Maddirela, Y K Banasavadi-Siddegowda, T-H Lai, Z Qamri, N K Jacob, D Sampath, S Mohanam, B Kaur, V K Puduvalli
Tumor recurrence in glioblastoma (GBM) is, in part, attributed to increased epithelial-to-mesenchymal transition (EMT) and enhanced tumor cell dissemination in adjacent brain parenchyma after ionizing radiation (IR). EMT is associated with aggressive behavior, increased stem-like characteristics and treatment resistance in malignancies; however, the underlying signaling mechanisms that regulate EMT are poorly understood. We identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and further determined its role in mesenchymal transition and radioresistance...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28534373/late-relapse-of-hodgkin-s-lymphoma-is-it-different-in-clinical-characteristics-and-outcome
#5
Olivera Markovic, Bosko Andjelic, Olivera Tarabar, Milena Todorovic, Branka Filipovic, Dejana Stanisavljevic, Jelena Bila, Darko Antic, Dragomir Marisavljevic, Biljana Mihaljevic
PURPOSE: The purpose of this study was to evaluate the clinical characteristics, prognostic factors, therapy and outcomes of patients with very late relapse (>5 years) of Hodgkin's lymphoma (HL). METHODS: We retrospectively reviewed the database of all relapsed patients with HL treated between 1999 and 2009 and compared the clinical characteristics and survival of patients who relapsed before and after 5 years of follow up. RESULTS: Among the group of 102 patients with relapsed HL 16 (15...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28528185/simvastatin-ameliorate-memory-deficits-and-inflammation-in-clinical-and-mouse-model-of-alzheimer-s-disease-via-modulating-the-expression-of-mir-106b
#6
Wenzhong Huang, Zhenyu Li, Liandong Zhao, Wei Zhao
BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research...
May 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28527574/nuclear-receptor-tlx-in-development-and-diseases
#7
Guoqiang Sun, Qi Cui, Yanhong Shi
The nuclear receptor TLX (NR2E1) is a transcription factor that is critical for neural development and adult neurogenesis through its actions in regulating neural stem cell proliferation, self-renewal, and fate determination. These roles are primarily executed by regulating TLX downstream target genes involved in myriad pathways such as cell cycle progression, RNA processing, angiogenesis, and senescence. Recent studies suggest that dysregulation of TLX pathways plays an important role in the pathogenesis of human neurological disorders and brain tumors...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28526577/changes-in-tumor-cell-heterogeneity-after-chemotherapy-treatment-in-a-xenograft-model-of-glioblastoma
#8
Alessandra M Welker, Brian D Jaros, Min An, Christine E Beattie
Glioblastoma (GBM) is a highly aggressive brain cancer with limited treatments and poor patient survival. GBM tumors are heterogeneous containing a complex mixture of dividing cells, differentiated cells, and cancer stem cells. It is unclear, however, how these different cell populations contribute to tumor growth or whether they exhibit differential responses to chemotherapy. Here we set out to address these questions using a zebrafish xenograft transplant model (Welker et al., 2016). We found that a small population of differentiated vimentin-positive tumor cells, but a majority of Sox2-positive putative cancer stem cells, were dividing during tumor growth...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28525381/the-cell-of-origin-dictates-the-temporal-course-of-neurofibromatosis-1-nf1-low-grade-glioma-formation
#9
Anne C Solga, Joseph A Toonen, Yuan Pan, Patrick J Cimino, Yu Ma, Guillaume A Castillon, Scott M Gianino, Mark H Ellisman, Da Yong Lee, David H Gutmann
Low-grade gliomas are one of the most common brain tumors in children, where they frequently form within the optic pathway (optic pathway gliomas; OPGs). Since many OPGs occur in the context of the Neurofibromatosis Type 1 (NF1) cancer predisposition syndrome, we have previously employed Nf1 genetically-engineered mouse (GEM) strains to study the pathogenesis of these low-grade glial neoplasms. In the light of the finding that human and mouse low-grade gliomas are composed of Olig2+ cells and that Olig2+ oligodendrocyte precursor cells (OPCs) give rise to murine high-grade gliomas, we sought to determine whether Olig2+ OPCs could be tumor-initiating cells for Nf1 optic glioma...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520736/the-bantam-microrna-acts-through-numb-to-exert-cell-growth-control-and-feedback-regulation-of-notch-in-tumor-forming-stem-cells-in-the-drosophila-brain
#10
Yen-Chi Wu, Kyu-Sun Lee, Yan Song, Stephan Gehrke, Bingwei Lu
Notch (N) signaling is central to the self-renewal of neural stem cells (NSCs) and other tissue stem cells. Its deregulation compromises tissue homeostasis and contributes to tumorigenesis and other diseases. How N regulates stem cell behavior in health and disease is not well understood. Here we show that N regulates bantam (ban) microRNA to impact cell growth, a process key to NSC maintenance and particularly relied upon by tumor-forming cancer stem cells. Notch signaling directly regulates ban expression at the transcriptional level, and ban in turn feedback regulates N activity through negative regulation of the Notch inhibitor Numb...
May 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28516286/establishment-of-a-tumor-sphere-cell-line-from-a-metastatic-brain-neuroendocrine-tumor
#11
Ryoichi Iwata, Masato Maruyama, Tomoki Ito, Yosuke Nakano, Yonehiro Kanemura, Taro Koike, Souichi Oe, Kunikazu Yoshimura, Masahiro Nonaka, Shosaku Nomura, Tetsuo Sugimoto, Hisao Yamada, Akio Asai
Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined...
May 17, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28515364/nicotinamide-metabolism-regulates-glioblastoma-stem-cell-maintenance
#12
Jinkyu Jung, Leo J Y Kim, Xiuxing Wang, Qiulian Wu, Tanwarat Sanvoranart, Christopher G Hubert, Briana C Prager, Lisa C Wallace, Xun Jin, Stephen C Mack, Jeremy N Rich
Metabolic dysregulation promotes cancer growth through not only energy production, but also epigenetic reprogramming. Here, we report that a critical node in methyl donor metabolism, nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brain. NNMT was preferentially expressed by mesenchymal glioblastoma stem cells (GSCs). NNMT depletes S-adenosyl methionine (SAM), a methyl donor generated from methionine. GSCs contained lower levels of methionine, SAM, and nicotinamide, but they contained higher levels of oxidized nicotinamide adenine dinucleotide (NAD+) than differentiated tumor cells...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514757/adhesion-and-stress-related-adaptation-of-glioma-radiochemoresistance-is-circumvented-by-%C3%AE-1-integrin-jnk-co-targeting
#13
Anne Vehlow, Erik Klapproth, Katja Storch, Ellen Dickreuter, Michael Seifert, Antje Dietrich, Rebecca Bütof, Achim Temme, Nils Cordes
Resistance of cancer stem-like and cancer tumor bulk cells to radiochemotherapy and destructive infiltration of the brain fundamentally influence the treatment efficiency to cure of patients suffering from Glioblastoma (GBM). The interplay of adhesion and stress-related signaling and activation of bypass cascades that counteract therapeutic approaches remain to be identified in GBM cells. We here show that combined inhibition of the adhesion receptor β1 integrin and the stress-mediator c-Jun N-terminal kinase (JNK) induces radiosensitization and blocks invasion in stem-like and patient-derived GBM cultures as well as in GBM cell lines...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513420/optimization-of-glioblastoma-mouse-orthotopic-xenograft-models-for-translational-research
#14
Susan M Irtenkauf, Susan Sobiechowski, Laura A Hasselbach, Kevin K Nelson, Andrea D Transou, Enoch T Carlton, Tom Mikkelsen, Ana C deCarvalho
Glioblastoma is an aggressive primary brain tumor predominantly localized to the cerebral cortex. We developed a panelofpatient-derived mouse orthotopic xenografts (PDOX) for preclinical drug studies by implanting cancer stem cells (CSC) cultured from fresh surgical specimens intracranially into 8-wk-old female athymic nude mice. Here we optimize the glioblastoma PDOX model by assessing the effect of implantation location on tumor growth, survival, and histologic characteristics. To trace the distribution of intracranial injections, toluidine blue dye was injected at 4 locations with defined mediolateral, anterioposterior, and dorsoventral coordinates within the cerebral cortex...
May 16, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28500786/dovitinib-enhances-temozolomide-efficacy-in-glioblastoma-cells
#15
Thatchawan Thanasupawat, Suchitra Natarajan, Amy Rommel, Aleksandra Glogowska, Hugo Bergen, Jerry Krcek, Marshall Pitz, Jason Beiko, Sherry Krawitz, Inder M Verma, Saeid Ghavami, Thomas Klonisch, Sabine Hombach-Klonisch
The multikinase inhibitor and FDA-approved drug Dovitinib (Dov) crosses the blood-brain-barrier and was recently used as single drug application in clinical trials for GB patients with recurrent disease. The Dov-mediated molecular mechanisms in GB cells are unknown. We used GB patient cells and cell lines to show that Dov downregulated the stem cell protein Lin28 and its target High Mobility Group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3(Tyr705) phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells...
May 13, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28487072/isocostunolide-inhibited-glioma-stem-cell-by-suppression-proliferation-and-inducing-caspase-dependent-apoptosis
#16
Zhi Dai, Shi-Rong Li, Pei-Feng Zhu, Lu Liu, Bei Wang, Ya-Ping Liu, Xiao-Dong Luo, Xu-Dong Zhao
Glioblastoma multiform (GBM) is a highly aggressive brain tumor with poor life expectancy, and glioma stem cells (GSCs) are a small population of tumor cells existed in GBM, in which GSCs response to drive GBM recurrence, invasion and contribute to the anti-cancer resistance. GSCs have been identified and developed as a therapeutic target for GBM and can be used in drugs screening. Isocostunolide is a natural sesquiterpenoid and contained abundant resource in medicinal plants, but the anti-cancer efficacies of it against GSCs are still unexplored...
April 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28486630/paired-related-homeobox-1-transactivates-dopamine-d2-receptor-to-maintain-propagation-and-tumorigenicity-of-glioma-initiating-cells
#17
Yamu Li, Wen Wang, Fangyu Wang, Qiushuang Wu, Wei Li, Xiaoling Zhong, Kuan Tian, Tao Zeng, Liang Gao, Ying Liu, Shu Li, Xiaobing Jiang, Guangwei Du, Yan Zhou
Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis. Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation, infiltration, and recurrence. GICs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors. Here, we find that paired related homeobox 1 (PRRX1), a homeodomain transcription factor that was previously reported to control skeletal development, is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation...
May 9, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28481046/human-neural-stem-cell-biodistribution-and-predicted-tumor-coverage-by-a-diffusible-therapeutic-in-a-mouse-glioma-model
#18
Michael E Barish, Kelsey Herrmann, Yang Tang, Siranush Argalian Herculian, Marianne Metz, Soraya Aramburo, Revathiswari Tirughana, Margarita Gutova, Alexander Annala, Rex A Moats, Leanne Goldstein, Russell C Rockne, Jennifer Gutierrez, Christine E Brown, Lucy Ghoda, Karen S Aboody
Engineered neural stem cells (NSCs) intrinsically migrating to brain tumors offer a promising mechanism for local therapeutic delivery. However, difficulties in quantitative assessments of NSC migration and in estimates of tumor coverage by diffusible therapeutics have impeded development and refinement of NSC-based therapies. To address this need, we developed techniques by which conventional serial-sectioned formalin-fixed paraffin-embedded (FFPE) brains can be analyzed in their entirety across multiple test animals...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28477133/dna-damage-response-in-human-stem-cells-and-neural-descendants
#19
Jason M Beckta, Bret R Adams, Kristoffer Valerie
Glial cells are crucial for the normal function of neurons and are intricately involved in the pathogenesis of neurodegenerative diseases as well as neurologic malignancies. A deeper understanding of the mechanisms by which glial cells influence the development of such pathologies will undoubtedly lead to new and improved therapeutic approaches. Commercially available human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), both of which can be differentiated into neural progenitors (NPs) and various neural cell lineages, have become widely used as sources for producing normal human central nervous system (CNS) cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28477008/combination-therapy-with-micellarized-cyclopamine-and-temozolomide-attenuate-glioblastoma-growth-through-gli1-down-regulation
#20
Yu-Jie Liu, Ying-Cong Ma, Wen-Jie Zhang, Zhen-Zhen Yang, De-Sheng Liang, Zhi-Fu Wu, Xian-Rong Qi
Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue and high recurrence rate. We studied the efficacy and related mechanisms of the combination of cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) and temozolomide (TMZ, the clinically most used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than Cyp solution in inhibiting GBM cells proliferation (3.77-fold against U87 MG cells and 3...
April 18, 2017: Oncotarget
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