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https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#1
Stephen C Mack, Paul A Northcott
Recent breakthroughs in next-generation sequencing technology and complementary genomic platforms have transformed our capacity to interrogate the molecular landscapes of human cancers, including childhood brain tumors. Numerous high-throughput genomic studies have been reported for the major histologic brain tumor entities diagnosed in children, including interrogations at the level of the genome, epigenome, and transcriptome, many of which have yielded essential new insights into disease biology. The nature of these discoveries has been largely platform dependent, exemplifying the usefulness of applying different genomic and computational strategies, or integrative approaches, to address specific biologic and/or clinical questions...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28638988/same-day-genomic-and-epigenomic-diagnosis-of-brain-tumors-using-real-time-nanopore-sequencing
#2
Philipp Euskirchen, Franck Bielle, Karim Labreche, Wigard P Kloosterman, Shai Rosenberg, Mailys Daniau, Charlotte Schmitt, Julien Masliah-Planchon, Franck Bourdeaut, Caroline Dehais, Yannick Marie, Jean-Yves Delattre, Ahmed Idbaih
Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e.g., for 1p/19q-codeletion or IDH mutations, to make an integrated histomolecular diagnosis. However, a plethora of sophisticated technologies is currently needed to assess different genomic and epigenomic alterations and turnaround times are in the range of weeks, which makes standardized and widespread implementation difficult and hinders timely decision making...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28635335/a-novel-synergetic-targeting-strategy-for-glioma-therapy-employing-borneol-combination-with-angiopep-2-modified-dox-loaded-pamam-dendrimer
#3
Shunping Han, Hongyue Zheng, Yanping Lu, Yue Sun, Anhao Huang, Weidong Fei, Xiaowei Shi, Xiuling Xu, Jingjing Li, Fanzhu Li
Glioma is the most common primary malignant brain tumor and the effect of chemotherapy is hampered by low permeability across the blood-brain-barrier (BBB). Borneol is a time-honored 'Guide' drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolized before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas)...
June 21, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28607809/rapid-response-of-brain-metastasis-to-crizotinib-in-a-patient-with-klc1-alk-fusion-and-met-gene-amplification-positive-non-small-cell-lung-cancer-a-case-report
#4
Peng Wang, Pei Xiao, Yingnan Ye, Pengpeng Liu, Lei Han, Li Dong, Chunhua She, Jinpu Yu
Non-small cell lung cancer (NSCLC) ranks as the leading cause of cancer-related death in the world. Brain metastasis (BM) is a common complication of NSCLC, with 25%-40% of patients developing BM during the course of the disease. A significant strategy of local disease control in the central nervous system is radiation therapy. With the development of precision medicine, the concept of treating lung cancer BM has gradually changed. In this case, we performed a surgical procedure to obtain enough tumor tissue for the detection of the target gene and other related experiments after the patient was informed...
May 2017: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/28600472/precision-medicine-in-pediatric-oncology-translating-genomic-discoveries-into-optimized-therapies
#5
Thai Hoa Tran, Avanthi Tayi Shah, Mignon L Loh
Survival of children with cancers has dramatically improved over the past several decades.  This success has been achieved through improvement of combined modalities in treatment approaches, intensification of cytotoxic chemotherapy for those with high-risk disease and refinement of risk stratification incorporating novel biologic markers in addition to traditional clinical and histologic features. Advances in cancer genomics have shed important mechanistic insights on disease biology and have identified "driver" genomic alterations, aberrant activation of signaling pathways, and epigenetic modifiers that can be targeted by novel agents...
June 9, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28574813/an-immunocompetent-mouse-model-of-human-glioblastoma
#6
Samantha Semenkow, Shen Li, Ulf D Kahlert, Eric H Raabe, Jiadi Xu, Antje Arnold, Miroslaw Janowski, Byoung Chol Oh, Gerald Brandacher, Jeff W M Bulte, Charles G Eberhart, Piotr Walczak
Orthotopic xenotransplantation studies represent the final stage in preclinical cancer research and could facilitate the implementation of precision medicine. To date, these xenografts have been tested in immunodeficient animals, but complete elimination of the adaptive immunity is a significant drawback. We present a method of efficient human glioblastoma (GBM) cell engraftment in adult mice with intact immune systems, mediated by a transient blockade of T-cell co-stimulation. Compared to transplants grown in immunodeficient hosts, the resulting tumors more accurately resemble the clinical pathophysiology of patient GBMs, which are characterized by blood-brain-barrier leakage and strong neo-vascularization...
May 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28565759/oral-administration-of-ampelopsin-protects-against-acute-brain-injury-in-rats-following-focal-cerebral-ischemia
#7
Xiao-Li Ye, Ling-Qun Lu, Wei Li, Qi Lou, Hong-Gang Guo, Qiao-Juan Shi
Ampelopsin (AMP) is isolated from the Chinese medicinal herb Ampelopsis grossedentata (Hand-Mazz) and has been associated with numerous biological and pharmacological activities. However, it is not clear whether AMP has a direct protective effect on cerebral ischemia reperfusion injury. Therefore, the present study investigated its role in acute brain injury following focal cerebral ischemia in rats. The current study induced transient focal cerebral ischemia by performing middle cerebral artery occlusion (MCAO) for 60 min, followed by 24 h of reperfusion...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28561225/feasibility-risk-profile-and-diagnostic-yield-of-stereotactic-biopsy-in-children-and-young-adults-with-brain-lesions
#8
Christina Hamisch, Tobias Blau, Katharina Klinger, Philipp Kickingereder, Daniel Ruess, Norbert Galldiks, Frank Berthold, Thorsten Simon, Stefan Grau, Maximilian I Ruge
Objective To evaluate the feasibility, safety, and diagnostic yield of stereotactic biopsy (SB) in children and adolescents with cerebral lesions. Methods We performed a systematic review of the literature and a retrospective analysis of all pediatric and adolescent patients who underwent SB for unclear brain lesions at our center. We collected patient and lesion-associated parameters, analysed the rate of procedural complications and diagnostic yield. Results Our institutional series consisted of 285 SBs in 269 children and young adults between 1989 and 2016 (median age, 9 (range 1-18) years)...
May 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28560582/towards-standardization-of-18-f-fet-pet-imaging-do-we-need-a-consistent-method-of-background-activity-assessment
#9
Marcus Unterrainer, Franziska Vettermann, Matthias Brendel, Adrien Holzgreve, Michael Lifschitz, Matthias Zähringer, Bogdana Suchorska, Vera Wenter, Ben M Illigens, Peter Bartenstein, Nathalie L Albert
BACKGROUND: PET with O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical (18)F-FET PET reading...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28555425/ethical-considerations-of-neuro-oncology-trial-design-in-the-era-of-precision-medicine
#10
REVIEW
Saksham Gupta, Timothy R Smith, Marike L Broekman
The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials...
May 29, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28545192/atypical-teratoid-rhabdoid-tumor-of-brain-a-clinicopathologic-study-of-eleven-patients-and-review-of-literature
#11
Nasir Ud Din, Abrar Barakzai, Aisha Memon, Sheema Hasan, Zubair Ahmad
Background: Atypical teratoid/ rhabdoid tumor (AT/RT) is a rare aggressive embryonal central nervous system (CNS) tumor of infancy and early childhood. Majority of the cases arise in the posterior fossa, and remaining in the cerebrum. Aims: To analyze the clinicopathologic features of AT/RT on a cohort of cases. Materials and methods: All reported cases of AT/RT at the Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH) from 2007 to 2016 were reviewed for clinical and pathological features...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28521703/recent-advances-in-antiepileptic-herbal-medicine
#12
Stephen M Manchishi
Epilepsy is one of the most common neurological disorders worldwide, with about 80 percent of cases thought to be in developing nations where it is mostly linked to superstition. Most cases of epilepsy are idiopathic, though brain injury, brain tumor, severe systemic infection and genetic mutations have been implicated in some cases. Anti-epileptic drugs (AEDs) currently in existence are not sufficient to contain the disorder. This is not only because of their limited availability and cost, but also their adverse side effects...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28514905/evodiamine-prevents-glioma-growth-induces-glioblastoma-cell-apoptosis-and-cell-cycle-arrest-through-jnk-activation
#13
Wen-Shin Wu, Chih-Chiang Chien, Kao-Hui Liu, Yen-Chou Chen, Wen-Ta Chiu
Evodiamine (EVO) is an active medicinal compound derived from the traditional herbal medicine Evodia rutaecarpa. It has been reported that evodiamine has several beneficial biological properties, including anticancer and anti-inflammatory activities. However, the in vitro and in vivo anticancer activities of EVO against the growth of glioblastoma cells remain undefined. EVO induced significant decreases in the viability of U87 and C6 glioma cells, but not of primary astrocytes, according with the occurrence of apoptotic characteristics including DNA ladders, caspase-3 and poly(ADP ribose) polymerase (PARP) protein cleavage, and hypodiploid cells...
May 18, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28507205/a-case-of-metastatic-atypical-neuroendocrine-tumor-with-alk-translocation-and-diffuse-brain-metastases
#14
Victoria E Wang, Lauren Young, Siraj Ali, Vincent A Miller, Anatoly Urisman, John Wolfe, Trever G Bivona, Bertil Damato, Shannon Fogh, Emily K Bergsland
A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28504360/oxygen-extraction-fraction-mapping-at-3-tesla-using-an-artificial-neural-network-a-feasibility-study
#15
Sebastian Domsch, Bettina Mürle, Sebastian Weingärtner, Jascha Zapp, Frederik Wenz, Lothar R Schad
PURPOSE: The oxygen extraction fraction (OEF) is an important biomarker for tissue-viability. MRI enables noninvasive estimation of the OEF based on the blood-oxygenation-level-dependent (BOLD) effect. Quantitative OEF-mapping is commonly applied using least-squares regression (LSR) to an analytical tissue model. However, the LSR method has not yet become clinically established due to the necessity for long acquisition times. Artificial neural networks (ANNs) recently have received increasing interest for robust curve-fitting and might pose an alternative to the conventional LSR method for reduced acquisition times...
May 14, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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/28481580/neurocognitive-deficits-in-children-with-chronic-health-conditions
#17
Bruce E Compas, Sarah S Jaser, Kristen Reeslund, Niral Patel, Janet Yarboi
Over 4 million children in the United States suffer from chronic health conditions, including cancer, sickle cell disease, and diabetes. Because of major advances in the early identification and treatment of these conditions, survival rates for these children continue to rise, and the majority now lives into adulthood. However, increases in survival have come with costs related to long-term effects of disease processes and treatments. Foremost among these consequences is impairment in brain development and neurocognitive function that may affect a substantial portion of children with chronic health conditions and follow many into adulthood...
May 2017: American Psychologist
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/28480589/quantification-and-tracking-of-genetically-engineered-dendritic-cells-for-studying-immunotherapy
#19
Amnon Bar-Shir, Lina Alon, Michael J Korrer, Hong Seo Lim, Nirbhay N Yadav, Yoshinori Kato, Arvind P Pathak, Jeff W M Bulte, Assaf A Gilad
PURPOSE: Genetically encoded reporters can assist in visualizing biological processes in live organisms and have been proposed for longitudinal and noninvasive tracking of therapeutic cells in deep tissue. Cells can be labeled in situ or ex vivo and followed in live subjects over time. Nevertheless, a major challenge for reporter systems is to identify the cell population that actually expresses an active reporter. METHODS: We have used a nucleoside analog, pyrrolo-2'-deoxycytidine, as an imaging probe for the putative reporter gene, Drosophila melanogaster 2'-deoxynucleoside kinase...
May 7, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28471848/l-borneol-induces-transient-opening-of-the-blood-brain-barrier-and-enhances-the-therapeutic-effect-of-cisplatin
#20
Yi Yin, Liu Cao, Hongfei Ge, Wangsheng Duanmu, Liang Tan, Jichao Yuan, Chen Tunan, Fei Li, Rong Hu, Fabao Gao, Hua Feng
The blood-brain barrier (BBB) protects the central nervous system from external insults by limiting substance diffusion through the endothelial interface. The presence of the BBB makes drug delivery in neurological disorders very challenging. Cisplatin has been shown to be cytotoxic to glioma cells, but substantial limitations exist in its clinical applications due to difficulties in penetration across the BBB. Here, we show that L-borneol, a messenger drug widely used in traditional Chinese medicine, can induce transient disruption of the BBB after 20 min of oral administration...
May 3, 2017: Neuroreport
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