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Pediatric brain cancer

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https://www.readbyqxmd.com/read/28717727/childhood-cancer-mortality-in-india-direct-estimates-from-a-nationally-representative-survey-of-childhood-deaths
#1
Sumit Gupta, Shaun K Morris, Wilson Suraweera, Lukasz Aleksandrowicz, Rajesh Dikshit, Prabhat Jha
PURPOSE: Although most children with cancer live in low- and middle-income countries, measurements of childhood cancer burden in such countries have been restricted to incidence rates from a few subnational cancer registries and mortality rates from vital statistics. We aimed to provide alternative burden estimates by using nationally representative longitudinal survey-derived mortality rates. METHODS: We examined cancer deaths in childhood (1 month to 14 years of age) in the Million Death Study, a cohort of > 27,000 pediatric deaths in India on the basis of enhanced verbal autopsies...
December 2016: Journal of Global Oncology
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#2
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28675683/pediatric-cancer-pathology-review-from-a-single-institution-neuropathology-expert-opinion-is-essential-for-accurate-diagnosis-of-pediatric-brain-tumors
#3
Zeina Merabi, Fouad Boulos, Teresa Santiago, Jesse Jenkins, Miguel Abboud, Samar Muwakkit, Nidale Tarek, Ghazi Zaatari, Sima Jeha, Hassan El-Solh, Raya Saab
BACKGROUND AND OBJECTIVES: Second pathology review has been reported to improve accuracy in oncologic diagnoses, including pediatric malignancies. We assessed the impact of second review on the diagnosis of pediatric malignancies at a tertiary care referral center in Beirut, Lebanon. METHODS: Pathology reports of patients treated at the Children's Cancer Institute in Lebanon were retrospectively reviewed for the period 2008-2016 and compared with same samples' diagnoses at St...
July 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28670142/prevalence-of-hypercalcemia-of-malignancy-among-pediatric-cancer-patients-in-the-uk-clinical-practice-research-datalink-database
#4
Susan Jick, Lin Li, Victor M Gastanaga, Alexander Liede, Rohini K Hernandez
BACKGROUND: The reported proportion of cancer patients who experience hypercalcemia of malignancy (HCM) is low, particularly in the pediatric population, ranging between <1% and 5%. HCM can be observed with any type of tumor in children and occurs most commonly with leukemia. While HCM is a potentially fatal condition, the prevalence of HCM is not well understood in pediatric cancer patients. METHODS: Using the UK Clinical Practice Research Datalink, we identified pediatric cancer patients with recorded corrected serum calcium (CSC) from 2003 through 2014...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28667671/smaller-hippocampal-subfield-volumes-predict-verbal-associative-memory-in-pediatric-brain-tumor-survivors
#5
Alexandra L Decker, Kamila U Szulc, Eric Bouffet, Suzanne Laughlin, M Mallar Chakravarty, Jovanka Skocic, Cynthia B de Medeiros, Donald J Mabbott
The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatments have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in twenty-nine pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and thirty healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short-term verbal memory...
July 1, 2017: Hippocampus
https://www.readbyqxmd.com/read/28640705/genomic-analysis-of-childhood-brain-tumors-methods-for-genome-wide-discovery-and-precision-medicine-become-mainstream
#6
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...
July 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28620009/recommendations-for-cancer-surveillance-in-individuals-with-rasopathies-and-other-rare-genetic-conditions-with-increased-cancer-risk
#7
REVIEW
Anita Villani, Mary-Louise C Greer, Jennifer M Kalish, Akira Nakagawara, Katherine L Nathanson, Kristian W Pajtler, Stefan M Pfister, Michael F Walsh, Jonathan D Wasserman, Kristin Zelley, Christian P Kratz
In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620008/pten-dicer1-fh-and-their-associated-tumor-susceptibility-syndromes-clinical-features-genetics-and-surveillance-recommendations-in-childhood
#8
REVIEW
Kris Ann P Schultz, Surya P Rednam, Junne Kamihara, Leslie Doros, Maria Isabel Achatz, Jonathan D Wasserman, Lisa R Diller, Laurence Brugières, Harriet Druker, Katherine A Schneider, Rose B McGee, William D Foulkes
PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620006/cancer-surveillance-in-gorlin-syndrome-and-rhabdoid-tumor-predisposition-syndrome
#9
REVIEW
William D Foulkes, Junne Kamihara, D Gareth R Evans, Laurence Brugières, Franck Bourdeaut, Jan J Molenaar, Michael F Walsh, Garrett M Brodeur, Lisa Diller
Gorlin syndrome and rhabdoid tumor predisposition syndrome (RTPS) are autosomal dominant syndromes associated with an increased risk of childhood-onset brain tumors. Individuals with Gorlin syndrome can manifest a wide range of phenotypic abnormalities, with about 5% of family members developing medulloblastoma, usually occurring in the first 3 years of life. Gorlin syndrome is associated with germline mutations in components of the Sonic Hedgehog pathway, including Patched1 (PTCH1) and Suppressor of fused (SUFU)SUFU mutation carriers appear to have an especially high risk of early-onset medulloblastoma...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28620005/cancer-and-central-nervous-system-tumor-surveillance-in-pediatric-neurofibromatosis-2-and-related-disorders
#10
REVIEW
D Gareth R Evans, Hector Salvador, Vivian Y Chang, Ayelet Erez, Stephan D Voss, Harriet Druker, Hamish S Scott, Uri Tabori
The neurofibromatoses consist of at least three autosomal-dominant inherited disorders: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis. For over 80 years, these conditions were inextricably tied together under generalized neurofibromatosis. In 1987, the localization of NF1 to chromosome 17q and NF2 (bilateral vestibular schwannoma) to 22q led to a consensus conference at Bethesda, Maryland. The two main neurofibromatoses, NF1 and NF2, were formally separated. More recently, the SMARCB1 and LZTR1 genes on 22q have been confirmed as causing a subset of schwannomatosis...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#11
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/28603776/actionable-molecular-biomarkers-in-primary-brain-tumors
#12
Verena Staedtke, Omar Dildar A Dzaye, Matthias Holdhoff
Recent genome-wide studies of malignancies of the central nervous system (CNS) have revolutionized our understanding of the biology of these tumors. This newly gained knowledge provides a wealth of opportunity for biomarker driven clinical research. To date, however, only few of the available molecular markers truly influence clinical decision-making and treatment. The most widely validated markers in neuro-oncology presently are: 1) MGMT promoter methylation as a prognostic and predictive marker in glioblastoma, 2) co-deletion of 1p and 19q differentiating oligodendrogliomas from astrocytomas, 3) IDH1/2 mutations, and 4) select pathway-associated mutations...
July 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28603224/proton-beam-therapy-for-pediatric-brain-tumor
#13
Masashi Mizumoto, Yoshiko Oshiro, Tetsuya Yamamoto, Hidehiro Kohzuki, Hideyuki Sakurai
Cancer is a major cause of childhood death, with central nervous system (CNS) neoplasms being the second most common pediatric malignancy, following hematological cancer. Treatment of pediatric CNS malignancies requires multimodal treatment using a combination of surgery, chemotherapy, and radiotherapy, and advances in these treatments have given favorable results and longer survival. However, treatment-related toxicities have also occurred, particularly for radiotherapy, after which secondary cancer, reduced function of irradiated organs, and retarded growth are significant problems...
June 9, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28600472/precision-medicine-in-pediatric-oncology-translating-genomic-discoveries-into-optimized-therapies
#14
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/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#15
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28591729/bmi-1-is-a-potential-therapeutic-target-in-diffuse-intrinsic-pontine-glioma
#16
Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B Stevenson, Maryam Fouladi, Rachid Drissi
Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells...
May 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28582547/the-torc1-2-inhibitor-tak228-sensitizes-atypical-teratoid-rhabdoid-tumors-to-cisplatin-induced-cytotoxicity
#17
Jeffrey A Rubens, Sabrina Z Wang, Antoinette Price, Melanie F Weingart, Sariah J Allen, Brent A Orr, Charles G Eberhart, Eric H Raabe
Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity...
June 3, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28570545/transplantation-of-zebrafish-pediatric-brain-tumors-into-immune-competent-hosts-for-long-term-study-of-tumor-cell-behavior-and-drug-response
#18
Mattie J Casey, Katarzyna Modzelewska, Daniela Anderson, James Goodman, Elena F Boer, Laura Jimenez, Douglas Grossman, Rodney A Stewart
Tumor cell transplantation is an important technique to define the mechanisms controlling cancer cell growth, migration, and host response, as well as to assess potential patient response to therapy. Current methods largely depend on using syngeneic or immune-compromised animals to avoid rejection of the tumor graft. Such methods require the use of specific genetic strains that often prevent the analysis of immune-tumor cell interactions and/or are limited to specific genetic backgrounds. An alternative method in zebrafish takes advantage of an incompletely developed immune system in the embryonic brain before 3 days, where tumor cells are transplanted for use in short-term assays (i...
May 17, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28521298/insulin-like-growth-factor-2-axis-supports-the-serum-independent-growth-of-malignant-rhabdoid-tumor-and-is-activated-by-microenvironment-stress
#19
Ting Li, Jin Wang, Pengfei Liu, Jiadong Chi, Han Yan, Lei Lei, Zexing Li, Bing Yang, Xi Wang
Malignant rhabdoid tumors (MRTs) are rare, lethal, pediatric tumors predominantly found in the kidney, brain and soft tissues. MRTs are driven by loss of tumor suppressor SNF5/INI1/SMARCB1/BAF47. The prognosis of MRT is poor using currently available treatments, so new treatment targets need to be identified to expand treatment options for patients experiencing chemotherapy resistance. The growth hormone insulin-like growth factor 2 (IGF2) signaling pathway is a promising target to overcome drug resistance in many cancers...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28510691/nf-%C3%AE%C2%BAb-upregulation-through-epigenetic-silencing-of-ldoc1-drives-tumor-biology-and-specific-immunophenotype-in-group-a-ependymoma
#20
Andrea M Griesinger, Davis A Witt, Sydney T Grob, Sabrina R Georgio Westover, Andrew M Donson, Bridget Sanford, Jean M Mulcahy Levy, Randall Wong, Daniel C Moreira, John A DeSisto, Ilango Balakrishnan, Lindsey M Hoffman, Michael H Handler, Kenneth L Jones, Rajeev Vibhakar, Sujatha Venkataraman, Nicholas K Foreman
Background.: Inflammation has been identified as a hallmark of high-risk Group A (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors drives an immune suppressive phenotype by polarizing infiltrating monocytes. This study determines the mechanism by which IL-6 is dysregulated in GpA EPN. Methods.: Twenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients and cell lines were used to validate transcriptomic findings...
May 16, 2017: Neuro-oncology
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