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medulloblastoma children

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https://www.readbyqxmd.com/read/28740935/effects-of-vertebral-body-sparing-proton-craniospinal-irradiation-on-the-spine-of-young-pediatric-patients-with-medulloblastoma
#1
Iain MacEwan, Brian Chou, Jeremy Moretz, Lilia Loredo, David Bush, Jerry D Slater
PURPOSE: To investigate the long-term effects of vertebral-body-sparing proton craniospinal irradiation (CSI) on the spine of young patients with medulloblastoma. METHODS AND MATERIALS: Six children between the ages of 3 and 5 years with medulloblastoma were treated with vertebral-body-sparing proton CSI after maximal safe resection. Radiation therapy was delivered in the supine position with posterior beams targeting the craniospinal axis, and the proton beam was stopped anterior to the thecal sac...
April 2017: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28717752/challenges-of-treating-childhood-medulloblastoma-in-a-country-with-limited-resources-20-years-of-experience-at-a-single-tertiary-center-in-malaysia
#2
Revathi Rajagopal, Sayyidatul Abd-Ghafar, Dharmendra Ganesan, Anita Zarina Bustam Mainudin, Kum Thong Wong, Norlisah Ramli, Vida Jawin, Su Han Lum, Tsiao Yi Yap, Eric Bouffet, Ibrahim Qaddoumi, Shekhar Krishnan, Hany Ariffin, Wan Ariffin Abdullah
PURPOSE: Pediatric medulloblastoma (MB) treatment has evolved over the past few decades; however, treating children in countries with limited resources remains challenging. Until now, the literature regarding childhood MB in Malaysia has been nonexistent. Our objectives were to review the demographics and outcome of pediatric MB treated at the University Malaya Medical Center between January 1994 and December 2013 and describe the challenges encountered. METHODS: Fifty-one patients with childhood MB were seen at University Malaya Medical Center...
April 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28689346/electromagnetic-navigation-guided-neuroendoscopic-removal-of-radiation-induced-intraforniceal-cavernoma-as-a-late-complication-of-medulloblastoma-treatment
#3
Petr Liby, J Zamecnik, M Kyncl, J Zackova, M Tichy
INTRODUCTION: Medulloblastoma is the most frequent malignant brain tumour in children. Radiation-induced cavernous haemangiomas (RICHs) are a known late complication of radiation exposure, especially in young children. CASE REPORT: We present a patient who underwent subtotal resection of posterior fossa medulloblastoma with subsequent chemotherapy and radiotherapy at the age of 10 years. A new lesion in the region of the left foramen of Monro appeared 16 years later...
July 8, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28662162/bkm120-induces-apoptosis-and-inhibits-tumor-growth-in-medulloblastoma
#4
Ping Zhao, Jacob Hall, Mary Durston, Austin Voydanoff, Elizabeth VanSickle, Shannon Kelly, Abhinav B Nagulapally, Jeffery Bond, Giselle Saulnier Sholler
Medulloblastoma (MB) is the most common malignant brain tumor in children, accounting for nearly 20 percent of all childhood brain tumors. New treatment strategies are needed to improve patient survival outcomes and to reduce adverse effects of current therapy. The phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) intracellular signaling pathway plays a key role in cellular metabolism, proliferation, survival and angiogenesis, and is often constitutively activated in human cancers, providing unique opportunities for anticancer therapeutic intervention...
2017: PloS One
https://www.readbyqxmd.com/read/28654202/socioeconomic-factors-affect-the-selection-of-proton-radiation-therapy-for-children
#5
Colette J Shen, Chen Hu, Matthew M Ladra, Amol K Narang, Craig E Pollack, Stephanie A Terezakis
BACKGROUND: Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. METHODS: This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy...
June 27, 2017: Cancer
https://www.readbyqxmd.com/read/28649600/oncolytic-herpes-virus-rrp450-shows-efficacy-in-orthotopic-xenograft-group-3-4-medulloblastomas-and-atypical-teratoid-rhabdoid-tumors
#6
Adam W Studebaker, Brian J Hutzen, Christopher R Pierson, Kellie B Haworth, Timothy P Cripe, Eric M Jackson, Jeffrey R Leonard
Pediatric brain tumors including medulloblastoma and atypical teratoid/rhabdoid tumor are associated with significant mortality and treatment-associated morbidity. While medulloblastoma tumors within molecular subgroups 3 and 4 have a propensity to metastasize, atypical teratoid/rhabdoid tumors frequently afflict a very young patient population. Adjuvant treatment options for children suffering with these tumors are not only sub-optimal but also associated with many neurocognitive obstacles. A potentially novel treatment approach is oncolytic virotherapy, a developing therapeutic platform currently in early-phase clinical trials for pediatric brain tumors and recently US Food and Drug Administration (FDA)-approved to treat melanoma in adults...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28625899/medulloblastoma-with-atypical-dynamic-imaging-changes-a-case-report-with-literature-review
#7
Shuang-Shuang Song, Jian-Hong Wang, Wei-Wei Fu, Ying Li, Qing-Lan Sui, Xue-Jun Liu
OBJECTIVE: We analyzed a case of medulloblastoma with atypical dynamic imaging changes retrospectively to summarized the atypical MRI features of medulloblastoma by reviewing the literature. METHODS: One atypical case of medulloblastoma in the cerebellar hemisphere confirmed by pathology was analyzed retrospectively, and the literature about it was reviewed. RESULTS: The radiologic findings of the patient were based on three examinations. The first examination showed that the cortex of the bilateral cerebellar hemisphere had diffuse nodular thickening, with a high signal on DWI imaging and significant enhancement...
June 15, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28623325/fluorescence-lifetime-imaging-microscopy-a-novel-diagnostic-tool-for-metastatic-cell-detection-in-the-cerebrospinal-fluid-of-children-with-medulloblastoma
#8
Sivan Gershanov, Shalom Michowiz, Helen Toledano, Gilad Yahav, Orit Barinfeld, Avraham Hirshberg, Haim Ben-Zvi, Gabriel Mircus, Mali Salmon-Divon, Dror Fixler, Nitza Goldenberg-Cohen
In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618224/design-synthesis-and-structure-activity-relationship-of-tetrahydropyrido-4-3-d-pyrimidine-derivatives-as-potent-smoothened-antagonists-with-in-vivo-activity
#9
Wenfeng Lu, Yongqiang Liu, Haikuo Ma, Jiyue Zheng, Sheng Tian, Zhijian Sun, Lusong Luo, Jiajun Li, Hongjian Zhang, Zeng-Jie Yang, Xiaohu Zhang
Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its nonlinear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility...
June 30, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#10
REVIEW
Atif A Ahmed, Abdalla D Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28605510/phase-i-study-of-oral-sonidegib-lde225-in-pediatric-brain-and-solid-tumors-and-a-phase-ii-study-in-children-and-adults-with-relapsed-medulloblastoma
#11
Mark W Kieran, Julia Chisholm, Michela Casanova, Alba A Brandes, Isabelle Aerts, Eric Bouffet, Simon Bailey, Sarah Leary, Tobey J MacDonald, Francoise Mechinaud, Kenneth J Cohen, Riccardo Riccardi, Warren Mason, Darren Hargrave, Stacey Kalambakas, Priya Deshpande, Feng Tai, Eunju Hurh, Birgit Geoerger
Background.: Sonidegib (LDE225) is a potent, selective Hedgehog (Hh) inhibitor of SMOOTHENED. This study explored the safety and pharmacokinetics (PK) of sonidegib in children with relapsed/recurrent tumors followed by a phase II trial in pediatric and adult patients with relapsed medulloblastoma (MB) to assess tumor response. Methods.: Pediatric patients aged ≥1-<18 years were included according to a Bayesian design starting at 372mg/m2 of continuous once daily oral sonidegib...
June 9, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28587051/evaluating-intensity-modulated-proton-therapy-relative-to-passive-scattering-proton-therapy-for-increased-vertebral-column-sparing-in-craniospinal-irradiation-in-growing-pediatric-patients
#12
Drosoula Giantsoudi, Joao Seco, Bree R Eaton, F Joseph Simeone, Hanne Kooy, Torunn I Yock, Nancy J Tarbell, Thomas F DeLaney, Judith Adams, Harald Paganetti, Shannon M MacDonald
PURPOSE: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. METHODS AND MATERIALS: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS)...
May 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28553259/a-retrospective-study-of-progression-free-and-overall-survival-in-pediatric-medulloblastoma-based-on-molecular-subgroup-classification-a-single-institution-experience
#13
Tao Jiang, Yuqi Zhang, Junmei Wang, Jiang Du, Raynald, Xiaoguang Qiu, Ying Wang, Chunde Li
BACKGROUND: Medulloblastoma (MB) has been classified into four core subgroups according to the transcriptional profile in recent years. However, some disagreement among researchers remains regarding the prognoses and most effective treatments of the different subgroups with different age distributions. OBJECTIVE: The objective of this study was to analyze MB prognosis in children population based on the classification of four molecular subgroups. METHODS: From January 2011 to January 2013, 84 consecutive MB patients aged underwent tumor removal at Beijing Tiantan Hospital...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28550392/treatment-of-pediatric-average-risk-medulloblastoma-using-craniospinal-irradiation-less-than-2500-cgy-and-chemotherapy-single-center-experience-in-korea
#14
Jong Hyung Yoon, Kyung Duk Park, Hyoung Jin Kang, Hyery Kim, Ji Won Lee, Seung-Ki Kim, Kyu-Chang Wang, Sung-Hye Park, Il Han Kim, Hee Young Shin
BACKGROUND: Although craniospinal irradiation (CSI) of 2340 cGy plus tumor booster with chemotherapy have been established as a standard treatment of childhood average-risk (AvR) medulloblastoma (MBL) in Western counties, there are a few recent reports in outcomes of AvR MBL using this strategy in Korean and other Asian children. We investigated the outcome of the Korean children with AvR MBL who were treated with CSI <2500 cGy and chemotherapy. METHODS: Between January 2001 and December 2010, clinical characteristics and outcomes of 42 patients who were diagnosed with AvR MBL postoperatively and treated with radiation including CSI <2500 cGy and chemotherapy in Seoul National University Children's Hospital were analyzed...
May 27, 2017: World Journal of Pediatrics: WJP
https://www.readbyqxmd.com/read/28545823/novel-molecular-subgroups-for-clinical-classification-and-outcome-prediction-in-childhood-medulloblastoma-a-cohort-study
#15
Edward C Schwalbe, Janet C Lindsey, Sirintra Nakjang, Stephen Crosier, Amanda J Smith, Debbie Hicks, Gholamreza Rafiee, Rebecca M Hill, Alice Iliasova, Thomas Stone, Barry Pizer, Antony Michalski, Abhijit Joshi, Stephen B Wharton, Thomas S Jacques, Simon Bailey, Daniel Williamson, Steven C Clifford
BACKGROUND: International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved...
July 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28536141/melk-and-ezh2-cooperate-to-regulate-medulloblastoma-cancer-stem-like-cell-proliferation-and-differentiation
#16
Hailong Liu, Qianwen Sun, Youliang Sun, Junping Zhang, Hongyu Yuan, Shuhuan Pang, Xueling Qi, Haoran Wang, Mingshan Zhang, Hongwei 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 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 subtype medulloblastoma...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28527006/analysis-of-surgical-and-mri-factors-associated-with-cerebellar-mutism
#17
Anjali Sergeant, Michelle Masayo Kameda-Smith, Branavan Manoranjan, Brij Karmur, JoAnn Duckworth, Tina Petrelli, Katey Savage, Olufemi Ajani, Blake Yarascavitch, M Constantine Samaan, Katrin Scheinemann, Cheryl Alyman, Saleh Almenawer, Forough Farrokhyar, Adam J Fleming, Sheila Kumari Singh, Nina Stein
The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. Therefore, we aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with individuals who did not acquire CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs)...
May 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28516074/an-updated-nationwide-epidemiology-of-primary-brain-tumors-in-republic-of-korea-2013
#18
Yun-Sik Dho, Kyu-Won Jung, Johyun Ha, Youngbeom Seo, Chul-Kee Park, Young-Joo Won, Heon Yoo
BACKGROUND: This report aims to provide accurate nationwide epidemiologic data on primary brain and central nervous system (CNS) tumors in the Republic of Korea. We updated the data by analyzing primary brain and CNS tumors diagnosed in 2013 using the data from the national cancer incidence database. METHODS: Data on primary brain and CNS tumors diagnosed in 2013 were collected from the Korean Central Cancer Registry. Crude and age-standardized rates were calculated in terms of gender, age, and histological type...
April 2017: Brain Tumor Research and Treatment
https://www.readbyqxmd.com/read/28508928/embryonal-tumors-in-canadian-children-less-than-36-months-of-age-results-from-the-canadian-pediatric-brain-tumor-consortium-cpbtc
#19
E Story, D L Johnston, U Bartels, A S Carret, B Crooks, D D Eisenstat, C Fryer, L Lafay-Cousin, V Larouche, B Wilson, S Zelcer, M Silva, J Brossard, E Bouffet, D L Keene
Embryonal tumors are a heterogeneous group of central nervous system (CNS) tumors whose subgroups have varying incidence and outcome. Despite these differences, they are often grouped as a single entity for study purposes. To date, there are no Canadian multi-institutional studies examining the incidence and outcome of all embryonal subtypes. The current study is an observational study reviewing embryonal tumors in all patients less than 36 months of age diagnosed with a CNS tumor in Canada from 1990 to 2005...
May 16, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28504719/novel-myc-driven-medulloblastoma-models-from-multiple-embryonic-cerebellar-cells
#20
D Kawauchi, R J Ogg, L Liu, D J H Shih, D Finkelstein, B L Murphy, J E Rehg, A Korshunov, C Calabrese, F Zindy, T Phoenix, Y Kawaguchi, J Gronych, R J Gilbertson, P Lichter, A Gajjar, M Kool, P A Northcott, S M Pfister, M F Roussel
Group3 medulloblastoma (MBG3) that predominantly occur in young children are usually associated with MYC amplification and/or overexpression, frequent metastasis and a dismal prognosis. Physiologically relevant MBG3 models are currently lacking, making inferences related to their cellular origin thus far limited. Using in utero electroporation, we here report that MBG3 mouse models can be developed in situ from different multipotent embryonic cerebellar progenitor cells via conditional expression of Myc and loss of Trp53 function in several Cre driver mouse lines...
May 15, 2017: Oncogene
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