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Medulloblastoma

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https://www.readbyqxmd.com/read/29352211/hdl-nanoparticles-targeting-sonic-hedgehog-subtype-medulloblastoma
#1
Jonathan B Bell, Jonathan S Rink, Frank Eckerdt, Jessica Clymer, Stewart Goldman, C Shad Thaxton, Leonidas C Platanias
Medulloblastoma is the most common paediatric malignant brain cancer and there is a need for new targeted therapeutic approaches to more effectively treat these malignant tumours, which can be divided into four molecular subtypes. Here, we focus on targeting sonic hedgehog (SHH) subtype medulloblastoma, which accounts for approximately 25% of all cases. The SHH subtype relies upon cholesterol signalling for tumour growth and maintenance of tumour-initiating cancer stem cells (CSCs). To target cholesterol signalling, we employed biomimetic high-density lipoprotein nanoparticles (HDL NPs) which bind to the HDL receptor, scavenger receptor type B-1 (SCARB1), depriving cells of natural HDL and their cholesterol cargo...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351917/a-novel-method-for-rapid-molecular-subgrouping-of-medulloblastoma
#2
Soledad Gómez, Alícia Garrido-Garcia, Laura Garcia-Gerique, Isadora Lemos, Mariona Suñol, Carmen de Torres, Marta Kulis, Sara Perez-Jaume, Angel M Carcaboso, Betty Luu, Mark W Kieran, Nada Jabado, Alexey Kozlenkov, Stella Dracheva, Vijay Ramaswamy, Volker Hovestadt, Pascal Johann, David T W Jones, Stefan M Pfister, Andrés Morales La Madrid, Ofelia Cruz, Michael D Taylor, Jose I Martín-Subero, Jaume Mora, Cinzia Lavarino
PURPOSE: The classification of medulloblastoma into WNT, SHH, Group 3 and Group 4 subgroups has become of critical importance for patient risk-stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma. EXPERIMENTAL DESIGN: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29349629/cerebellum-from-development-to-disease-the-8th-international-symposium-of-the-society-for-research-on-the-cerebellum-and-ataxias
#3
EDITORIAL
Hassan Marzban, Mario Manto, Jean Mariani
In recent years, there has been tremendous growth in research on cerebellar motor and non-motor functions. Cerebellum is particularly involved in the spectrum of neurodevelopmental diseases. The 8th International Symposium of the Society for Research on the Cerebellum and Ataxia (SRCA) was held in Winnipeg, Manitoba, (Canada) on May 24-26, 2017. The main theme of the 8th International Symposium was "Development of the Cerebellum and Neurodevelopmental Disorders." Advances in genetics, epigenetic, cerebellar neurogenesis, axonogenesis and gliogenesis, cerebellar developmental disorders including autism spectrum disorders (ASD), neuroimaging, cerebellar ataxias, medulloblastoma, and clinical investigation of cerebellar diseases were presented...
January 18, 2018: Cerebellum
https://www.readbyqxmd.com/read/29348431/a-synthetic-combinatorial-approach-to-disabling-deviant-hedgehog-signaling
#4
C-W Fan, N Yarravarapu, H Shi, O Kulak, J Kim, C Chen, L Lum
Mutations in components of the Hedgehog (HH) signal transduction pathway are found in the majority of basal cell carcinoma (BCC) and medulloblastoma incidents. Cancerous cells with intrinsic or acquired resistance to antagonists targeting the seven transmembrane effector Smoothened (SMO) frequently invoke alternative mechanisms for maintaining deviant activity of the GLI DNA binding proteins. Here we introduce a chemical agent that simultaneously achieves inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC) family...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29344238/sophoridine-suppresses-cell-growth-in-human-medulloblastoma-through-foxm1-nf-%C3%AE%C2%BAb-and-ap-1
#5
Zhensong Yue, Tongguo Si, Zhanyu Pan, Wenfeng Cao, Zhuchen Yan, Zhansheng Jiang, Huaqiang Ouyang
Sophoridine is an alkaloid extracted from Sophora alopecuroides that has extensive pharmacological actions. In the present study, the effect of sophoridine on cell growth of human medulloblastoma and its mechanism were investigated. Human medulloblastoma D283-Med cells were incubated with 0, 0.5, 1 or 2 mg/ml sophoridine for 24, 48 or 72 h. Cell proliferation and cytotoxicity were analyzed using MTT and lactate dehydrogenase assays, respectively. Next, analyses of cell apoptosis and caspase-3/8 activity were performed using flow cytometry or spectrophotometry, respectively...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343221/a-case-of-molecularly-profiled-extraneural-medulloblastoma-metastases-in-a-child
#6
Nahla Ali Mobark, Musa Al-Harbi, Othman Mosleh, Sandro Santagata, Matija Snuderl, Malak Abedalthagafi
BACKGROUND: Extraneural metastases are relatively rare manifestations of medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group three MYCN-amplified medulloblastoma. He received multimodal chemotherapy consisting of gross total resection followed by postoperative craniospinal radiation and adjuvant chemotherapy. The patient developed extraneural metastases 4 months after the end of therapy. Literature review identifies the poor prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases; we review the current limitations and future directions of medulloblastoma treatment options...
January 17, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29340047/inhibition-of-polo-like-kinase-4-plk4-a-new-therapeutic-option-for-rhabdoid-tumors-and-pediatric-medulloblastoma
#7
Simone Treiger Sredni, Anders W Bailey, Amreena Suri, Rintaro Hashizume, Xingyao He, Nundia Louis, Tufan Gokirmak, David R Piper, Daniel M Watterson, Tadanori Tomita
Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal tumors. They are the most common malignant CNS tumors in infants below 6 months of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum and are the most frequent pediatric malignant brain tumors. Despite the advances in recent years, especially for the most favorable molecular subtypes of MB, the prognosis of patients with embryonal tumors remains modest with treatment related toxicity dreadfully high. Therefore, new targeted therapies are needed...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29336639/intellectual-educational-and-situation-based-social-outcome-in-adult-survivors-of-childhood-medulloblastoma
#8
Virginie Kieffer, Mathilde P Chevignard, Georges Dellatolas, Stephanie Puget, Frederic Dhermain, Jacques Grill, Dominique Valteau-Couanet, Christelle Dufour
PURPOSE: To investigate intellectual and situation-based social outcome and educational achievement in adult survivors of childhood medulloblastoma and analyse factors influencing outcome Methods: We collected demographic, medical and cognitive data, and social and educational outcome at a mean time since the end of treatments of 14.9 years in 58 adults, aged 19-35 years, consecutively treated in a single cancer center between 1989 and 2005. RESULTS: Ten survivors had severe intellectual disability, 12 were still studying, 23 had a regular employment and 13 were unemployed...
January 16, 2018: Developmental Neurorehabilitation
https://www.readbyqxmd.com/read/29329453/response-to-harreld-re-response-assessment-in-medulloblastoma-and-leptomeningeal-seeding-tumors-recommendations-from-the-response-assessment-in-pediatric-neuro-oncology-committee
#9
Katherine E Warren, Gilbert Vezina, Tina Y Poussaint, Monika Warmuth-Metz, Roger J Packer, Mark W Kieran
No abstract text is available yet for this article.
January 10, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29329452/comment-on-response-assessment-in-medulloblastoma-and-leptomeningeal-seeding-tumors-recommendations-from-the-response-assessment-in-pediatric-neuro-oncology-committee
#10
https://www.readbyqxmd.com/read/29325939/liponeurocytoma-of-the-cerebello-pontine-angle
#11
Carmela Chiaramonte, Sylvain Rabaste, Timothee Jacquesson, David Meyronet, François Cotton, Emmanuel Jouanneau, Moncef Berhouma
Liponeurocytoma is a very rare tumor classified as grade II (neuronal and mixed neuronal-glial tumors) according to 2016 WHO classification of Tumors of the Central Nervous System. The median age is 50-years-old and the most frequent location is the posterior cranial fossa especially within the cerebellar hemispheres; those arising in the cerebellopontine angle are exceptional. We herein report the clinical, radiological and pathological characteristics of a cerebellopontine angle liponeurocytoma in a 35-year-old woman...
January 8, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29321089/silencing-of-e3-ubiquitin-ligase-rnf8-enhances-ionizing-radiation-sensitivity-of-5-medulloblastoma-cells-by-promoting-the-deubiquitination-of-pcna
#12
Fei Li, Bin Liu, Xiaolan Zhou, Quan Xu
DNA damage response induced by ionizing radiation (IR) is an important event that involved in the sensitivity and efficiency of radiotherapy in human medulloblastoma. RNF8 is a E3 ubiquitin ligase and has key roles in the process of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the DNA damage repair induced by IR exposure in medulloblastoma cells. We found that the levels of RNF8 were significantly up-regulated by γ-ray irradiation in a dose-dependent manner in medulloblastoma cells, and colocalized with γ-H2AX, a sensitive marker of DNA double strand break induced by γ-ray radiation...
January 10, 2018: Oncology Research
https://www.readbyqxmd.com/read/29319727/risk-factors-for-the-prognosis-of-pediatric-medulloblastoma-a-retrospective-analysis-of-40-cases
#13
Jianzhong Yu, Rui Zhao, Wei Shi, Hao Li
No abstract text is available yet for this article.
December 2017: Clinics
https://www.readbyqxmd.com/read/29315108/review-of-molecular-classification-and-treatment-implications-of-pediatric-brain-tumors
#14
Ana S Guerreiro Stucklin, Vijay Ramaswamy, Craig Daniels, Michael D Taylor
PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors...
February 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29314442/lncrna-cdkn2bas-rs2157719-genetic-variant-contributes-to-medulloblastoma-predisposition
#15
Yi-Dong Chen, Nasha Zhang, Xiao-Guang Qiu, Jupeng Yuan, Ming Yang
BACKGROUND: How germline single nucleotide polymorphisms are involved in the etiology of medulloblastoma remans poorly understood. We hypothesized that CCDKN2A/B rs1063192 and rs4977756 and also the long noncoding RNA (lncRNA) CDKN2BAS rs2157719 glioma susceptibility polymorphisms identified by genome-wide association studies may contribute to medulloblastoma predisposition. METHODS: To test this hypothesis, we genotyped these genetic variants among 160 medulloblastoma patients and 443 health controls in a Chinese population...
January 4, 2018: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29309676/survival-impact-of-postoperative-radiotherapy-timing-in-pediatric-and-adolescent-medulloblastoma
#16
Alexander L Chin, Everett J Moding, Sarah S Donaldson, Iris C Gibbs, Scott G Soltys, Susan M Hiniker, Erqi L Pollom
Background: Radiation therapy (RT) remains a critical component of multimodality treatment for medulloblastoma. Traditionally, clinicians strive to start RT within 4-5 weeks of surgery, but the optimal timing after surgery remains unclear. Methods: Using the National Cancer Database, we identified pediatric and adolescent patients with medulloblastoma treated with curative-intent surgery, RT, and chemotherapy. Factors associated with early or delayed RT were identified using Pearson chi-squared tests...
January 4, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29303460/erratum-differential-patterns-of-metastatic-dissemination-across-medulloblastoma-subgroups
#17
Vijay Ramaswamy
No abstract text is available yet for this article.
January 5, 2018: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29302048/diagnostic-challenges-in-a-child-with-early-onset-desmoplastic-medulloblastoma-and-homozygous-variants-in-msh2-and-msh6
#18
Julia Taeubner, Katharina Wimmer, Martine Muleris, Olivier Lascols, Chrystelle Colas, Christine Fauth, Triantafyllia Brozou, Joerg Felsberg, Jasmin Riemer, Michael Gombert, Sebastian Ginzel, Jessica I Hoell, Arndt Borkhardt, Michaela Kuhlen
Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR) genes. The spectrum of CMMRD-associated tumours is very broad and many CMMRD patients additionally display signposting non-neoplastic features, most frequently café-au-lait macules and other pigmentation alterations. We report on a 13-month-old girl suspected of having CMMRD due to a desmoplastic medulloblastoma and a striking skin pigmentation that included multiple café-au-lait macules, hypopigmented areas and Mongolian spots...
January 4, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29285383/effect-of-o6-methylguanine-dna-methyltransferase-methylation-in-medulloblastoma
#19
Tomoko Kurimoto, Akihide Kondo, Ikuko Ogino, Junya Fujimura, Atsushi Arakawa, Hajime Arai, Toshiaki Shimizu
Medulloblastoma is a highly malignant brain tumor that predominately affects children and requires multimodal treatment, including chemotherapy with alkylating agents. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent studies demonstrated that MGMT promoter methylation suppresses the expression of MGMT and is associated with favorable outcomes of malignant glioma patients. However, the MGMT methylation status and its prognostic impact on medulloblastoma have not been fully elucidated to date...
December 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29280516/suppression-of-stat3-nh2-terminal-domain-chemosensitizes-medulloblastoma-cells-by-activation-of-protein-inhibitor-of-activated-stat3-via-de-repression-by-microrna-21
#20
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
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