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https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#1
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28212737/gene-delivery-of-apoptin-derived-peptide-using-an-adeno-associated-virus-vector-inhibits-glioma-and-prolongs-animal-survival
#2
Xiuli Zhong, Hengyu Zhao, Songhe Liang, DanYang Zhou, Wenjia Zhang, Lijie Yuan
Glioblastoma (GBM) is the most common malignant brain tumor in adults. We designed an adeno-associated virus (AAV) vector for intracranial delivery of the secreted HSP70-targeted peptide APOPTIN derived from Apoptin to GBM tumors. We applied this therapy to GBM models using human U87MG glioma cells and GBM xenograft models in mice. In U87MG and U251MG cells, conditioned medium from AAV2-apoptin-derived peptide (ADP)-expressing cells induced 83% and 78% cell death. In mice bearing intracranial U87MG tumors treated with AAV2-ADP, treatment resulted in a significant decrease in tumor growth and longer survival in mice bearing orthotopic invasive GBM brain tumors...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212562/overexpression-of-mir-29a-reduces-the-oncogenic-properties-of-glioblastoma-stem-cells-by-downregulating-quaking-gene-isoform-6
#3
Zhuo Xi, Ping Wang, Yixue Xue, Chao Shang, Xiaobai Liu, Jun Ma, Zhiqing Li, Zhen Li, Min Bao, Yunhui Liu
Glioblastoma is the most common type of malignant primary brain tumor and has high recurrence and lethality rates. Glioblastoma stem cells (GSCs), a subpopulation of glioblastoma cells, may promote rapid tumor recurrence and therapy resistance. Because altered microRNA (miR) expression in GSCs may lead to glioblastoma progression, we assessed the effects of miR-29a expression on the oncogenic behavior of GSCs. MiR-29a expression was lower in GSCs than non-GSCs, and overexpression of miR-29a in GSCs inhibited cell proliferation, migration and invasion, but promoted apoptosis...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212546/precursor-n-cadherin-mediates-glial-cell-line-derived-neurotrophic-factor-promoted-human-malignant-glioma
#4
Ye Xiong, Liyun Liu, Shuang Zhu, Baole Zhang, Yuxia Qin, Ruiqin Yao, Hao Zhou, Dian Shuai Gao
As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#5
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28208698/advances-in-molecular-imaging-of-locally-delivered-targeted-therapeutics-for-central-nervous-system-tumors
#6
REVIEW
Umberto Tosi, Christopher S Marnell, Raymond Chang, William C Cho, Richard Ting, Uday B Maachani, Mark M Souweidane
Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28205381/the-clinical-significance-of-equivocal-findings-on-spinal-mri-in-children-with-medulloblastoma
#7
Julie Bennett, Ramy Ashmawy, Vijay Ramaswamy, Derek Stephens, Eric Bouffet, Normand Laperriere, Michael Taylor, Manohar Shroff, Ute Bartels
BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification...
February 16, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28205096/pharmacological-effects-of-asiatic-acid-in-glioblastoma-cells-under-hypoxia
#8
Flourina Kumar Thakor, Ka-Wai Wan, Philip John Welsby, Gail Welsby
Glioblastoma multiforme is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood-brain barrier, novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28204824/dna-methylation-mediated-caspase-8-downregulation-is-associated-with-anti-apoptotic-activity-and-human-malignant-glioma-grade
#9
Yueqiu Teng, Yu-Cui Dong, Zhaoyu Liu, Yan Zou, Hui Xie, Yu Zhao, Jun Su, Fenglin Cao, Hua Jin, Huan Ren
The methylation-mediated silencing of tumor suppressors, including key apoptosis-related genes plays an important role in the pathogenesis and therapeutic resistance in human cancer. In this study, we aimed to elucidate the role and mechanisms of resistance to apoptosis with caspase-8 gene downregulation in human malignant glioma. Reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) were used to examine caspase-8 expressoin at the mRNA level and gene methylation status in normal brain tissue, glioma tissue and cancer cell lines...
February 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203179/malignant-phyllodes-tumor-presenting-in-bone-brain-lungs-and-lymph-nodes
#10
Eric D Johnson, Evin Gulbahce, Joseph McNally, Saundra S Buys
INTRODUCTION: Phyllodes tumors (PTs) are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. CASE: A 66-year-old female presented with a large breast mass...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28197638/cobalt-chloride-treatment-induces-autophagic-apoptosis-in-human-glioma-cells-via-a-p53-dependent-pathway
#11
Bor-Chin Cheng, Jui-Tai Chen, Shun-Tai Yang, Chung-Ching Chio, Shing-Hwa Liu, Ruei-Ming Chen
Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration- and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells...
January 25, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197403/network-plasticity-and-intraoperative-mapping-for-personalized-multimodal-management-of-diffuse-low-grade-gliomas
#12
REVIEW
Cristina Diana Ghinda, Hugues Duffau
Gliomas are the most frequent primary brain tumors and include a variety of different histological tumor types and malignancy grades. Recent achievements in terms of molecular and imaging fields have created an unprecedented opportunity to perform a comprehensive interdisciplinary assessment of the glioma pathophysiology, with direct implications in terms of the medical and surgical treatment strategies available for patients. The current paradigm shift considers glioma management in a comprehensive perspective that takes into account the intricate connectivity of the cerebral networks...
2017: Frontiers in Surgery
https://www.readbyqxmd.com/read/28194092/paradoxes-of-the-ephb1-receptor-in-malignant-brain-tumors
#13
REVIEW
Wenqiang Wei, Hongju Wang, Shaoping Ji
Eph receptors are a subfamily of receptor tyrosine kinases. Eph receptor-mediated forward and ephrin ligand-mediated reverse signalings are termed bidirectional signaling. Increasing evidence shows that Eph/ephrin signaling regulates cell migration, adhesion, morphological changes, differentiation, proliferation and survival through cell-cell communication. Some recent studies have started to implicate Eph/ephrin signaling in tumorigenesis, metastasis, and angiogenesis. Previous studies have shown that EphB1 receptor and its ephrin ligands are expressed in the central nervous system...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28192888/computed-tomography-morphologic-features-of-pulmonary-adenocarcinoma-with-brain-bone-metastasis
#14
Ki-Eun Hwang, Su-Jin Oh, Chul Park, Se-Jeong Jeon, Jeong-Mi Lee, Byong-Ki Cha, Kwon-Ha Yoon, Eun-Taik Jeong, Hak-Ryul Kim
Background/Aims: Brain and bone metastases are common in patients with lung cancer. The development of metastasis is associated with poor survival in lung cancer patients. Although tumor morphologic features on radiographs are routinely assessed for differentiation between benign and malignant lung nodules, they are not used to predict metastasis. We assessed morphologic features of pulmonary adenocarcinomas with brain/bone metastasis on computed tomography (CT) to identify related factors for metastasis...
February 15, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28192386/spectrum-of-magnetic-resonance-imaging-features-in-unilateral-optic-tract-dysfunction
#15
Kristopher M Kowal, Francisco F Rivas Rodriguez, Ashok Srinivasan, Jonathan D Trobe
BACKGROUND: Optic tract dysfunction may be the predominant or only clinical manifestation of an intracranial disorder including mass legion, ischemic infarct, inflammatory disease, and trauma. Documentation of the neuroimaging features of these lesions is limited to reports mostly published before the availability of MRI. This study was undertaken to document the spectrum of MRI features in patients presenting with optic tract dysfunction. METHODS: A retrospective study from 2004 to 2015 at a single tertiary care neuro-ophthalmology service of 24 patients who had unilateral optic tract dysfunction defined by a homonymous hemianopia and a relative afferent pupil defect that could not be attributed to optic neuropathy or retinopathy...
March 2017: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/28191774/novel-peripherally-derived-neural-like-stem-cells-as-therapeutic-carriers-for-treating-glioblastomas
#16
Alexander Birbrair, Anirudh Sattiraju, Dongqin Zhu, Gilberto Zulato, Izadora Batista, Van T Nguyen, Maria Laura Messi, Kiran Kumar Solingapuram Sai, Frank C Marini, Osvaldo Delbono, Akiva Mintz
Glioblastoma (GBM), an aggressive grade IV astrocytoma, is the most common primary malignant adult brain tumor characterized by extensive invasiveness, heterogeneity, and angiogenesis. Standard treatment options such as radiation and chemotherapy have proven to be only marginally effective in treating GBM because of its invasive nature. Therefore, extensive efforts have been put forth to develop tumor-tropic stem cells as viable therapeutic vehicles with potential to treat even the most invasive tumor cells that are harbored within areas of normal brain...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28190444/management-of-neuro-oncologic-emergencies
#17
J T Jo, D Schiff
Patients with brain tumors and systemic malignancies are subject to diverse neurologic complications that require urgent evaluation and treatment. These neurologic conditions are commonly due to the tumor's direct effects on the nervous system, such as cerebral edema, increased intracranial pressure, seizures, spinal cord compression, and leptomeningeal metastases. In addition, neurologic complications can develop as a result of thrombocytopenia, coagulopathy, hyperviscosity syndromes, infection, immune-related disorders, and adverse effects of treatment...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28188727/apoptin-gene-delivery-by-the-functionalized-polyamidoamine-pamam-dendrimer-derivatives-induces-cell-death-of-u87-mg-glioblastoma-cells
#18
Yoonhee Bae, Hyang-Shuk Rhim, Seulgi Lee, Kyung Soo Ko, Jin Han, Joon Sig Choi
Malignant glioma is the most common and aggressive form of primary brain tumor in adults. In this study, we describe the efficacy of nonviral gene delivery carriers, histidine and arginine or histidine and lysine grafted PAMAM dendrimers (PAMAM-H-R and PAMAM-H-K), in delivering a therapeutic, a tumor-selective killer gene, apoptin, using human glioma cells (U87-MG) and newborn human dermal fibroblast (NB-HDF) cells. We analyzed transfection efficiency using luciferase (Luc) and a pDNA encoding for enhanced fluorescent protein (EGFP), and assessed cell viability in both cells...
February 7, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28187000/malat1-is-a-prognostic-factor-in-glioblastoma-multiforme-and-induces-chemoresistance-to-temozolomide-through-suppressing-mir-203-and-promoting-thymidylate-synthase-expression
#19
Wei Chen, Xin-Ke Xu, Jun-Liang Li, Kuan-Kei Kong, Hui Li, Cheng Chen, Jing He, Fangyu Wang, Ping Li, Xiao-Song Ge, Fang-Cheng Li
Glioblastoma multiforme (GBM) is the most malignant brain tumor with limited therapeutic options. Temozolomide (TMZ) is a novel cytotoxic agent used as first-line chemotherapy for GBM, however, some individual cells can't be isolated for surgical resection and show treatment-resistance, thus inducing poor prognosis. By using the HiSeq sequencing and bioinformatics methods, we identified lncRNAs showing different expression levels in TMZ-resistant and non-resistant patients. RT-qPCR was then performed in tissues and serum samples, and lncRNA MALAT1 was finally identified to show considerable discriminating potential to identify responding patients from non-responding patients...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28185119/biallelic-brca2-mutations-in-two-black-south-african-children-with-fanconi-anaemia
#20
Candice Feben, Careni Spencer, Anneline Lochan, Nakita Laing, Karen Fieggen, Engela Honey, Tasha Wainstein, Amanda Krause
Fanconi anaemia (FA) is a genotypically and phenotypically heterogeneous genetic condition, characterized cytogenetically by chromosomal instability and breakage secondary to impaired DNA repair mechanisms. Affected individuals typically manifest growth restriction and congenital physical abnormalities and most progress to hematological disease including bone marrow aplasia. A rare genetic subtype of FA (FA-D1) is caused by biallelic mutations in the BRCA2 gene. Affected individuals manifest severe congenital anomalies and significant pigmentary changes and are additionally at risk for early onset leukemia and certain solid organ malignancies, including Wilms tumors and brain tumors...
February 9, 2017: Familial Cancer
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