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medulloblastoma IV

Oren J Becher, Stephen W Gilheeney, Yasmin Khakoo, David C Lyden, Sofia Haque, Kevin C De Braganca, Jill M Kolesar, Jason T Huse, Shakeel Modak, Leonard H Wexler, Kim Kramer, Ivan Spasojevic, Ira J Dunkel
BACKGROUND: The PI3K/AKT/mTOR pathway is aberrantly activated in many pediatric solid tumors including gliomas and medulloblastomas. Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolimus (mTOR inhibitor) is more potent at inhibiting the axis than either agent alone. We conducted this study to assess pharmacokinetics and identify the maximum tolerated dose for the combination. PROCEDURE: We performed a standard 3+3 phase I, open-label, dose-escalation study in patients with recurrent/refractory pediatric solid tumors...
December 30, 2016: Pediatric Blood & Cancer
Ryuya Yamanaka, Azusa Hayano, Tomohiko Kanayama
By conducting a systemic search of the PubMed database, we performed a comprehensive literature review to characterize secondary gliomas following radiotherapy treatment and to determine the most appropriate treatment strategy. Our analysis included 296 cases of radiation-induced gliomas. The primary lesion was characterized as a hematological malignancy in 104 cases (35.1 %), pituitary adenoma in 35 (11.8 %), craniopharyngioma in 19 (6.4 %), medulloblastoma in 38 (12.8 %), germ cell tumor in 13 (4.3 %), low-grade glioma in 28 (9...
October 5, 2016: Neurosurgical Review
Su-Hua Huang, Jin-Cherng Lien, Chao-Jung Chen, Yu-Ching Liu, Ching-Ying Wang, Chia-Fong Ping, Yu-Fong Lin, An-Cheng Huang, Cheng-Wen Lin
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, has five genotypes (I, II, III, IV, and V). JEV genotype I circulates widely in some Asian countries. However, current JEV vaccines based on genotype III strains show low neutralizing capacities against genotype I variants. In addition, JE has no specific treatment, except a few supportive treatments. Compound CW-33, an intermediate synthesized derivative of furoquinolines, was investigated for its antiviral activities against JEV in this study...
August 24, 2016: International Journal of Molecular Sciences
Ralph Salloum, Trent R Hummel, Shiva Senthil Kumar, Kathleen Dorris, Shaoyu Li, Tong Lin, Vinay M Daryani, Clinton F Stewart, Lili Miles, Tina Young Poussaint, Charles Stevenson, Stewart Goldman, Girish Dhall, Roger Packer, Paul Fisher, Ian F Pollack, Maryam Fouladi, James Boyett, Rachid Drissi
Telomerase activation is critical in many cancers including central nervous system (CNS) tumors. Imetelstat is an oligonucleotide that binds to the template region of the RNA component of telomerase, inhibiting its enzymatic activity. We conducted an investigator-sponsored molecular biology (MB) and phase II study to estimate inhibition of tumor telomerase activity and sustained responses by imetelstat in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, high-grade glioma (HGG) or ependymoma undergoing resection received one dose of imetelstat as a 2-h intravenous infusion at 285 mg/m(2), 12-24 h before surgery...
September 2016: Journal of Neuro-oncology
Fatima Bilqees, Khaleeq Samina, Tahir Mohammad, Khaleeq-uz-Zamaan
BACKGROUND: Recent studies, including a comprehensive study by National Cancer Institute, have shown that a significant increase in the incidence of childhood brain tumours makes them the most common paediatric tumour. The objectives of this study were to determine the frequency of central nervous system tumours in paediatric age group (0-12 years), and to segregate various morphologic types according to WHO classification. METHODS: The study included consecutive cases of central nervous system tumours diagnosed in children in the histopathology department at Federal Government Polyclinic, PGMI, Islamabad, during a period of 4...
January 2016: Journal of Ayub Medical College, Abbottabad: JAMC
Navneet Singla, Ankur Kapoor, Amey Savardekar, B D Radotra, Debjyoti Chatterjee, Sunil K Gupta
BACKGROUND: Tumors arising from cerebellar peduncle are extremely rare and behave aggressively. The inclusion of these into either cerebellar or brainstem gliomas is contentious. CASE DESCRIPTION: We performed clinicopathological review of three patients treated at our institute and surveyed the literature for previous such reported cases. Mean duration of symptoms in our patients was 2 weeks. Subtotal tumor resection was performed in two patients while the third underwent stereotactic biopsy followed by chemoradiotherapy...
2016: Surgical Neurology International
Annika K Wefers, Sven Lindner, Johannes H Schulte, Ulrich Schüller
LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors...
February 2017: Cerebellum
Martha Assimakopoulou, Christina Androutsopoulou, Vassiliki Zolota, John Matsoukas
The pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of hypoxia-inducible Factor-1α (HIF-1α). HIF-1α is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1α interaction is inhibited resulting in the nuclear accumulation of HIF-1α. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1α and degradation of pVHL. The aim of this study was to estimate immunohistochemically the expression levels of HIF-1α and pVHL, in relation to Hsp90, in different types of human brain tumors (42 gliomas, 9 medulloblastomas, and 38 meningiomas) using specific antibodies...
May 2016: Histology and Histopathology
Sameera Ezzat, Mohamed Kamal, Nada El-Khateeb, Mohamed El-Beltagy, Hala Taha, Amal Refaat, Madeha Awad, Sherif Abouelnaga, Mohamed Saad Zaghloul
Central nervous system (CNS) tumors are the most frequent solid tumors in children and adolescents. The epidemiology of these tumors differs in areas of the world. However, very little data is available in the low/middle income countries (LMIC). The aim of this study is to describe the characteristics of primary childhood brain tumors treated at a leading LMIC pediatric cancer hospital and its difference from that in other countries. One thousand one hundred fourteen children and adolescent having CNS tumors were treated in the largest pediatric cancer hospital in the Middle East during a period of 5½ years...
January 2016: Journal of Neuro-oncology
Rancés Blanco, Yisel Quintana, Damián Blanco, Mercedes Cedeño, Charles E Rengifo, Milagros Frómeta, Martha Ríos, Enrique Rengifo, Adriana Carr
The expression of N-glycolylneuraminic acid forming the structure of gangliosides and/or other glycoconjugates (Hanganutziu-Deicher antigen) in human has been considered as a tumor-associated antigen. Specifically, some reports of 14F7 Mab (a highly specific Mab raised against N-glycolyl GM3 ganglioside) reactivity in human tumors have been recently published. Nevertheless, tumors of epithelial origin have been mostly evaluated. The goal of the present paper was to evaluate the immunohistochemical recognition of 14F7 Mab in different human tumors of neuroectodermal, mesodermal, and epithelial origins using an immunoperoxidase staining method...
2013: Journal of Biomarkers
Deanna Mitchell, Genevieve Bergendahl, William Ferguson, William Roberts, Timothy Higgins, Takamaru Ashikaga, Mike DeSarno, Joel Kaplan, Jacqueline Kraveka, Don Eslin, Alyssa Vander Werff, Gina K Hanna, Giselle L Saulnier Sholler
BACKGROUND: The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. PROCEDURE: Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ...
January 2016: Pediatric Blood & Cancer
Kim S Bull, Christina Liossi, Janet L Peacock, Ho Ming Yuen, Colin R Kennedy
BACKGROUND: We aimed to identify a brief screening measure for detection of cognitive deficit in children treated for cerebellar tumors that would be useful in clinical practice. METHODS: A sample of 72 children, aged 8-14 years, and within 3 years post diagnosis for standard-risk medulloblastoma (n = 37) or low-grade cerebellar astrocytoma (n = 35) and 38 children in a nontumor group were assessed using teacher-, parent-, and child-report of the Behavior Rating Inventory of Executive Function (BRIEF), Strengths and Difficulties Questionnaire (SDQ), and Pediatric Quality of Life Inventory (PedsQL)...
December 2015: Neuro-oncology
Tryggve Lundar, Bernt Johan Due-Tønnessen, Arild Egge, Bård Krossnes, Einar Stensvold, Paulina Due-Tønnessen, Petter Brandal
OBJECT: The aim of this study is to delineate the long-term results for patients going through surgery for pediatric brain tumors in the first 6 months of life. METHODS: Thirty consecutive children (1-182 days old) who underwent primary resection for a brain tumor during the years 1973-2012 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily life were scored according to the Barthel index...
December 2015: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Renata G Medina, David P Dempsher, Karen M Gauvain, Thomas J Geller, Samer K Elbabaa
Medulloblastoma is a malignant embryonal tumor that arises in the cerebellum and invades the fourth ventricle, often resulting in obstructive hydrocephalus. Patients typically present with symptoms related to increased intracranial pressure and cerebellar dysfunction. The authors report a rare case of classic medulloblastoma with central precocious puberty (CPP) as its only presenting symptom. A 7-year-old boy with no prior history of medulloblastoma presented with Tanner Stage IV testicular enlargement and a 4-month history of acne and pubic hair...
September 2015: Journal of Neurosurgery. Pediatrics
Ayman Samkari, Jason White, Roger Packer
Medulloblastoma is the most common malignant brain tumor of childhood. It is currently stratified into four molecular variants through the advances in transcriptional profiling. They include: wingless, sonic hedgehog (SHH), Group III, and Group IV. The SHH group is characterized by constitutive activation of the SHH signaling pathway, and genetically characterized by mutations in patched homolog 1 (PTCH1) or other downstream pathway mutations. SHH inhibitors have become of great clinical interest in treating SHH-driven medulloblastoma...
2015: Expert Review of Neurotherapeutics
Iman Sidhom, Enas El Nadi, Hala Taha, Naglaa Elkinaai, Mohamed S Zaghloul, Alaa Younes, Rania Labib, Mohamed Sabry
BACKGROUND: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. AIM: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. PATIENTS AND METHODS: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010...
June 2015: Journal of the Egyptian National Cancer Institute
Xing Kang, Rong Chen, Jie Zhang, Gang Li, Peng-Gao Dai, Chao Chen, Hui-Juan Wang
BACKGROUND: Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status. MATERIALS AND METHODS: IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Stefan Rieken, Juliane Rieber, Stephan Brons, Daniel Habermehl, Harald Rief, Lena Orschiedt, Katja Lindel, Klaus J Weber, Jürgen Debus, Stephanie E Combs
Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA)...
May 2015: Journal of Radiation Research
Tommaso Tartaglione, Giana Izzo, Andrea Alexandre, Annibale Botto, Giuseppe Maria Di Lella, Simona Gaudino, Massimo Caldarelli, Cesare Colosimo
PURPOSE: Olivary degeneration is due to many posterior cranial fossa (PCF) lesions affecting the dentato-rubro-olivary pathway, also known as Guillain-Mollaret triangle. Triangle damage results in hyperexcitation and consequently in hypertrophy of the inferior olivary nucleus (ION). The aim of our study was to evaluate the incidence of magnetic resonance (MR) imaging changes in the ION after surgery in a large cohort of paediatric patients and to determine their correlation with tumour grade...
May 2015: La Radiologia Medica
Leslie L Muldoon, Y Jeffrey Wu, Michael A Pagel, Edward A Neuwelt
Decreasing oxidative damage with the antioxidant agent N-acetylcysteine (NAC) can block the side effects of chemotherapy, but may diminish anti-tumor efficacy. We tested the potential for interactions of high dose NAC against a minimally effective cisplatin chemotherapy regimen in rat models of human pediatric cancers. Athymic rats received subcutaneous implantation of human SK-N-AS neuroblastoma cells or intra-cerebellar implantation of human D283-MED medulloblastoma cells. Rats were untreated or treated with cisplatin (3 or 4 mg/kg IV) with or without NAC (1,000 mg/kg IV) 30 min before or 4 h after cisplatin treatment...
February 2015: Journal of Neuro-oncology
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