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Medulloblastoma

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https://www.readbyqxmd.com/read/27917595/societal-preferences-in-the-treatment-of-pediatric-medulloblastoma-balancing-risk-of-death-and-quality-of-life
#1
Amir Khakban, Tima Mohammadi, Larry D Lynd, Don Mabbott, Eric Bouffet, Louise Gastonguay, Zafar Zafari, David Malkin, Michael Taylor, Carlo A Marra
PURPOSE: Medulloblastoma is the most prevalent childhood brain cancer. Children with medulloblastoma typically receive a combination of surgery, radiation, and chemotherapy. The survival rate is high but survivors often have sequelae from radiotherapy of the entire developing brain and spinal cord. Ongoing genetic studies have suggested that decreasing the dose of radiation might be possible among children with favorable molecular variants; however, this may result in an increased disease recurrence...
December 4, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27917302/characterization-of-the-blood-brain-barrier-in-pediatric-central-nervous-system-neoplasms
#2
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/27904083/novel-sulfonamide-derivatives-carrying-a-biologically-active-3-4-dimethoxyphenyl-moiety-as-vegfr-2-inhibitors
#3
Mostafa Mohammed Ghorab, Mansour Sulaiman Alsaid, Yassin Mohammed Nissan, Abdelkader Elbadawy Ashour, Abdullah Abdulalrahman Al-Mishari, Ashok Kumar, Sheikh Fayaz Ahmed
Novel sulfonamides 3-19 with a biologically active 3,4-dimethoxyphenyl moiety were designed and synthesized. The structures of the synthesized compounds were established using elemental analyses, IR, (1)H-NMR, (13)C-NMR spectral data and mass spectroscopy. All the synthesized compounds were evaluated for their in vitro anticancer activity against four cancer cell lines, namely human hepatocellular carcinoma (HepG2), human medulloblastoma (Daoy), human cervical cancer (HeLa), and human colon cancer (HT-29), by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and dasatinib as the reference drug...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27900530/erratum-to-the-dna-methyltransferase-inhibitor-zebularine-exerts-antitumor-effects-and-reveals-batf2-as-a-poor-prognostic-marker-for-childhood-medulloblastoma
#4
Augusto Faria Andrade, Kleiton Silva Borges, Veridiana Kiill Suazo, Lenisa Geron, Carolina Alves Pereira Corrêa, Angel Mauricio Castro-Gamero, Elton José Rosas de Vasconcelos, Ricardo Santos de Oliveira, Luciano Neder, José Andres Yunes, Simone Dos Santos Aguiar, Carlos Alberto Scrideli, Luiz Gonzaga Tone
No abstract text is available yet for this article.
November 29, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27899820/inhibition-of-hedgehog-dependent-tumors-and-cancer-stem-cells-by-a-newly-identified-naturally-occurring-chemotype
#5
Paola Infante, Romina Alfonsi, Cinzia Ingallina, Deborah Quaglio, Francesca Ghirga, Ilaria D'Acquarica, Flavia Bernardi, Laura Di Magno, Gianluca Canettieri, Isabella Screpanti, Alberto Gulino, Bruno Botta, Mattia Mori, Lucia Di Marcotullio
Hedgehog (Hh) inhibitors have emerged as valid tools in the treatment of a wide range of cancers. Indeed, aberrant activation of the Hh pathway occurring either by ligand-dependent or -independent mechanisms is a key driver in tumorigenesis. The smoothened (Smo) receptor is one of the main upstream transducers of the Hh signaling and is a validated target for the development of anticancer compounds, as underlined by the FDA-approved Smo antagonist Vismodegib (GDC-0449/Erivedge) for the treatment of basal cell carcinoma...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27889018/posterior-fossa-tumors
#6
REVIEW
Lara A Brandão, Tina Young Poussaint
Pediatric brain tumors are the leading cause of death from solid tumors in childhood. The most common posterior fossa tumors in children are medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on computed tomography (CT) and conventional MR (cMR) imaging may provide important clues to the most likely diagnosis. Moreover, information obtained from advanced MR imaging techniques increase diagnostic confidence and help distinguish between different histologic tumor types...
February 2017: Neuroimaging Clinics of North America
https://www.readbyqxmd.com/read/27866682/-adolescent-and-young-adults-ayas-brain-tumor-national-web-conference-on-behalf-of-anocef-go-aja-and-sfce-societies
#7
Didier Frappaz, Marie-Pierre Sunyach, Emilie Le Rhun, Marie Blonski, Valérie Laurence, Alice Bonneville Levard, Hugues Loiseau, David Meyronnet, Arnaud Callies, F Laigle-Donadey, Cecile Faure Conter
: The skills of adult versus pediatric neuro-oncologists are not completely similar though additive. Because the tumors and their protocols are different and the tolerance and expected sequelae are specific. Multidisciplinary meetings including adult and pediatric neuro-oncologists are warranted to share expertise. Since 2008, a weekly national web based conference was held in France. Any patient with the following criteria could be discussed: Adolescent and Young Adults aged between 15 and 25 years, and any adult with a pediatric type pathology, including medulloblastoma, germ cell tumors, embryonic tumors, ependymoma, pilocytic astrocytoma...
November 17, 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/27864705/the-clinical-and-financial-impact-of-a-pediatric-surgical-neuro-oncology-clinical-trial
#8
Eric M Thompson, Sridharan Gururangan, Gerald Grant, Duane Mitchell, John H Sampson
Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requiring the biopsy or resection of recurrent medulloblastoma or PNET for enrollment. Inpatient financial and clinical volume information was collected during the 3 years of trial enrollment and the years preceding and following it. The primary endpoints were the difference in direct contribution margin (DCM), or net gain, of study and non-study patients and the difference in surgical volume during the study and non-study periods...
November 18, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27863192/treatment-of-children-and-adolescents-with-metastatic-medulloblastoma-and-prognostic-relevance-of-clinical-and-biologic-parameters
#9
André O von Bueren, Rolf-Dieter Kortmann, Katja von Hoff, Carsten Friedrich, Martin Mynarek, Klaus Müller, Tobias Goschzik, Anja Zur Mühlen, Nicolas Gerber, Monika Warmuth-Metz, Niels Soerensen, Frank Deinlein, Martin Benesch, Isabella Zwiener, Robert Kwiecien, Andreas Faldum, Udo Bode, Gudrun Fleischhack, Volker Hovestadt, Marcel Kool, David Jones, Paul Northcott, Joachim Kuehl, Stefan Pfister, Torsten Pietsch, Stefan Rutkowski
Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed. Results In 123 eligible patients (median age, 8.2 years old; median follow-up, 5.38 years), 5-year event-free survival (EFS) and overall survival (OS) were 62% (95% CI, 52 to 72) and 74% (95% CI, 66 to 82), respectively...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27834469/the-expression-of-fat1-is-associated-with-overall-survival-in-children-with-medulloblastoma
#10
Jianzhong Yu, Hao Li
PURPOSE: The FAT1 gene is involved in some cancers; however, its role in medulloblastoma is less clear. This study investigated the effects of FAT1 expression on the prognosis of medulloblastoma patients. METHODS: Whole exome sequencing was undertaken in 40 medulloblastoma patient samples. FAT1 mRNA and protein expression levels in normal and brain tumor tissues were determined by fluorescence quantitative PCR and immunohistochemistry, respectively. The association of FAT1 expression with overall survival (OS) was examined by Kaplan-Meier curve analysis with a log-rank test...
November 8, 2016: Tumori
https://www.readbyqxmd.com/read/27830395/glutamine-for-the-treatment-of-vincristine-induced-neuropathy-in-children-and-adolescents-with-cancer
#11
Stephen Sands, Elena J Ladas, Kara M Kelly, Michael Weiner, Meiko Lin, Deborah Hughes Ndao, Amie Dave, Linda T Vahdat, Julia Glade Bender
BACKGROUND: Vincristine is an integral treatment component of many childhood tumors with potentially dose-limiting sensory and/or motor neuropathy. Results from a pilot study on the incidence of vincristine-induced peripheral neuropathy (VIPN) as well as the efficacy and safety of glutamine in reducing signs and symptoms of VIPN in children with cancer are presented. METHODS: Fifty-six patients between the ages of 5-21 with newly diagnosed leukemia, lymphoma, extracranial solid tumor or medulloblastoma and expected to receive a minimum cumulative dose of 6 mg/m(2) of vincristine over a 30-week period were eligible...
November 9, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/27823583/norrin-frizzled4-signalling-in-the-preneoplastic-niche-blocks-medulloblastoma-initiation
#12
Erin A Bassett, Nicholas Tokarew, Ema A Allemano, Chantal Mazerolle, Katy Morin, Alan J Mears, Brian McNeill, Randy Ringuette, Charles Campbell, Sheila Smiley, Neno T Pokrajac, Adrian M Dubuc, Vijay Ramaswamy, Paul A Northcott, Marc Remke, Philippe P Monnier, David Potter, Kim Paes, Laura L Kirkpatrick, Kenneth J Coker, Dennis S Rice, Carol Perez-Iratxeta, Michael D Taylor, Valerie A Wallace
The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch(+/-) mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB...
November 8, 2016: ELife
https://www.readbyqxmd.com/read/27815386/pten-signaling-in-the-postnatal-perivascular-progenitor-niche-drives-medulloblastoma-formation
#13
Guo Zhu, Sherri L Rankin, Jon D Larson, Xiaoyan Zhu, Lionel Ml Chow, Chunxu Qu, Jinghui Zhang, David W Ellison, Suzanne J Baker
Loss of the tumor suppressor gene PTEN exerts diverse outcomes on cancer in different developmental contexts. To gain insight into the effect of its loss on outcomes in the brain, we conditionally inactivated the murine Pten gene in neonatal neural stem/progenitor cells. Pten inactivation created an abnormal perivascular proliferative niche in the cerebellum that persisted in adult animals but did not progress to malignancy. Proliferating cells showed undifferentiated morphology and expressed the progenitor marker Nestin but not Math1, a marker of committed granule neuron progenitors...
November 4, 2016: Cancer Research
https://www.readbyqxmd.com/read/27812533/data-on-the-number-and-frequency-of-scientific-literature-citations-for-established-medulloblastoma-cell-lines
#14
D P Ivanov, D A Walker, B Coyle, A M Grabowska
This article collates information about the number of scientific articles mentioning each of the established medulloblastoma cell lines, derived through a systematic search of Web of Science, Scopus and Google Scholar in 2016. The data for each cell line have been presented as raw number of citations, percentage share of the total citations for each search engine and as an average percentage between the three search engines. In order to correct for the time since each cell line has been in use, the raw citation data have also been divided by the number of years since the derivation of each cell line...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27810591/design-synthesis-and-biological-evaluation-of-structurally-modified-isoindolinone-and-quinazolinone-derivatives-as-hedgehog-pathway-inhibitors
#15
Deepak Bhattarai, Joo Hyun Jung, Seunghyeon Han, Hankyu Lee, Soo Jin Oh, Hyuk Wan Ko, Kyeong Lee
The Hedgehog (Hh) signaling pathway is associated with diverse aspects of cellular events, such as cell migration, proliferation, and differentiation throughout embryonic development and tissue patterning. An abnormal Hh signaling pathway is linked to numerous human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB), lung cancer, prostate cancer, and ovarian cancer, and it is therefore a promising target in cancer therapy. Using a structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biologically evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells...
October 19, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27804208/birth-weight-and-subsequent-risk-of-childhood-primary-brain-tumors-an-updated-meta-analysis
#16
Anne Dahlhaus, Peggy Prengel, Logan Spector, Dawid Pieper
BACKGROUND: Primary brain tumors are common in childhood, but the etiology is largely unclear. As studies on birth weight as a risk factor for the occurrence of histologically specified tumors have been inconclusive, we decided to update a 2008 meta-analysis on the subject. METHODS: A search strategy was performed in Medline and EMBASE for the period 2007-2016. We included six new studies and performed further subgroup analyses for medulloblastoma and primitive neuroectodermal tumors (PNETs)...
November 2, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27803059/atr-maintains-chromosomal-integrity-during-postnatal-cerebellar-neurogenesis-and-is-required-for-medulloblastoma-formation
#17
Patrick Y Lang, Gouri J Nanjangud, Marina Sokolsky-Papkov, Christine Shaw, Duhyeong Hwang, Joel S Parker, Alexander V Kabanov, Timothy R Gershon
Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report that ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co-deletions of either p53 or Bax and Bak prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth...
November 1, 2016: Development
https://www.readbyqxmd.com/read/27802424/dual-role-of-the-integrated-stress-response-in-medulloblastoma-tumorigenesis
#18
Sarrabeth Stone, Yeung Ho, Xiting Li, Stephanie Jamison, Heather P Harding, David Ron, Wensheng Lin
In response to endoplasmic reticulum (ER) stress, activation of pancreatic ER kinase (PERK) coordinates an adaptive program known as the integrated stress response (ISR) by phosphorylating translation initiation factor 2α (eIF2α). Phosphorylated eIF2α is quickly dephosphorylated by the protein phosphatase 1 and growth arrest and DNA damage 34 (GADD34) complex. Data indicate that the ISR can either promote or suppress tumor development. Our previous studies showed that the ISR is activated in medulloblastoma in both human patients and animal models, and that the decreased ISR via PERK heterozygous deficiency attenuates medulloblastoma formation in Patched1 heterozygous deficient (Ptch1+/-) mice by enhancing apoptosis of pre-malignant granule cell precursors (GCPs) during cell transformation...
September 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27801730/multifocal-supra-and-infratentorial-medulloblastoma-in-an-adult-histologic-immunohistochemical-and-molecular-evaluation-of-a-rare-case-and-review-of-the-literature
#19
Ali G Saad, Vladimir Balik, Aatif Parvez, Siraj M El Jamal
Multifocal medulloblastomas (MMBs) in adults are exceedingly rare with only 5 reported cases to date. Medulloblastoma in adult differ from its childhood counterpart by being more often lateral in location, desmoplastic in morphology, and better in clinical prognosis. Little is known, however, about the characteristic features of MMB. This is particularly true for their molecular profiles. To date, molecular characteristics of multifocal medulloblastoma have been reported only once. Here, we present the second case of multifocal medulloblastoma along with its detailed morphology, imaging features, and molecular profiles with a critical review of the literature...
October 31, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27799929/the-high-prevalence-of-functional-complement-defects-induced-by-chemotherapy
#20
Mischa P Keizer, Angela M Kamp, Cathelijn Aarts, Judy Geisler, Huib N Caron, Marianne D van de Wetering, Diana Wouters, Taco W Kuijpers
INTRODUCTION: To date, oncology patients are more dependent on non-cellular host defense against pathogens due to intensive (chemo)therapy-related bone marrow suppression. Since data on complement functionality in oncology patients are limited, we aimed to investigate the innate complement function in relation to the type of malignancy and therapy in a longitudinal cohort of patients. METHODS: A large single-center, prospective non-intervention study was conducted, in which blood samples were taken from patients before, during, and after treatment with chemotherapy and/or subsequent admittance for (febrile) neutropenia...
2016: Frontiers in Immunology
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