Advancing Treatments for Pediatric Craniopharyngioma (ATPC): Preliminary Assessment of the Cyst Fluid Inflammatory Milieu

推进小儿颅咽管瘤 (ATPC) 的治疗：囊肿液炎症环境的初步评估

• 批准号: 9232507
• 负责人: Todd C Hankinson
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-06 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9232507
• 关键词: Activities of Daily Living; Acute; Animal Model; Animals; Appearance; Astrocytes; Award; Basic Science; Behavior; Bioinformatics; Biological Assay; Blindness; CTNNB1 gene; Cell Proliferation; Cells; Child; Childhood; Childhood Brain Neoplasm; Childhood Craniopharyngioma; Chronic; Chronic Disease; Cognitive; Collaborations; Colorado; Craniopharyngioma; Curative Surgery; Cyst; Cyst Fluid; Cytokine Gene; DNA Sequence Alteration; Data; Databases; Economic Burden; Economics; Environment; Ependymoma; Epithelial; FDA approved; Face; Family; Flow Cytometry; Gene Chips; Gene Expression; Gene Expression Profiling; Genes; Germ cell tumor; Goals; Growth; Histologic; Human; Human Resources; Hypothalamic structure; IL8 gene; Immune; Immunobiology; Impairment; In Vitro; Incidence; Individual; Infiltration; Inflammation; Inflammatory; Inflammatory Response; Injury; Institution; Interdisciplinary Study; Interleukin 6 Receptor; Interleukin-1 beta; Interleukin-10; Interleukin-6; International; Investigation; K-Series Research Career Programs; Laboratories; Lesion; Letters; Life Expectancy; Location; Malignant Neoplasms; Measures; Mediator of activation protein; Membrane; Mentors; Methods; Microarray Analysis; Microglia; Minority; Neurologic; Neurologic Deficit; Neurological outcome; Neurosecretory Systems; Neurosurgeon; Normal Cell; North America; Obesity; Oncogenic; Panhypopituitarism; Paracrine Communication; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Pilocytic Astrocytoma; Play; Population; Positioning Attribute; Principal Investigator; Process; Production; Publications; Quality of life; Research; Research Personnel; Research Project Grants; Rhabdoid Tumor; Risk; Role; Sampling; Schools; Source; Specimen; Structure; Supratentorial; Systems Biology; TNF gene; Techniques; The University of Colorado Cancer Center; Therapeutic; Tissues; Training; Tumor Tissue; United States National Institutes of Health; Universities; Vascular Diseases; Work; cell type; cytokine; disability; experimental study; functional outcomes; improved; inflammatory milieu; interest; keratinocyte; monocyte; mortality; mouse model; multidisciplinary; neoplastic cell; novel; novel therapeutics; online resource; overexpression; response; social; therapeutic target; transcriptome; transcriptome sequencing; tumor

Project Summary The principal investigator for this Small Research Grant is a pediatric neurosurgeon with specific interest in improving the neurological and functional outcomes (e.g. quality of life, school performance, activities of daily living) for children who are afflicted with adamantinomatous craniopharyngioma (ACP). This neurologically devastating tumor, due to its low mortality rate, forces children and their families to face a lifetime of chronic and profound disability. As a junior investigator, the PI has developed, and leads, North America's only consortium dedicated to the study of pediatric ACP, Advancing Treatment for Pediatric Craniopharyngioma (ATPC). The goal of this award is to determine whether pilot data that Dr. Hankinson derived from ACP specimens merits further investigation with animal models, and potentially human trials. Analysis of cytokine expression from ACP cyst fluid indicated a unique proinflammatory profile, when compared to another cyst- forming pediatric brain tumor, Pilocytic Astrocytoma. This raises the possibility that FDA approved medications that specifically target IL-6/IL-6 receptor, a critical mediator of the proinflammatory pathway, could control ACP cyst growth. This could reveal a novel therapeutic option for children with ACP, either through improved tumor control or by facilitating safer curative surgery. By leveraging the University of Colorado's NIH-supported interdisciplinary research centers, this small project will identify which cellular component of ACP is responsible for the secretion of proinflammatory cytokines and, further, if IL-6/IL-6R blockade mitigates this process. Dr. Hankinson works in an environment that is ideal for the completion of this work. He works very closely with Dr. Nicholas Foreman, who is one of the primary mentors on his KL2 career development award. Dr. Foreman is a well-established senior investigator and leader in research regarding the immunobiology of pediatric brain tumors, most notably ependymoma. Dr. Hankinson has also undertaken formal training in bioinformatics during his KL2 award period, which resulted in a strong relationship with Dr. Aik-Choon Tan, Director of the Translational Bioinformatics and Cancer Systems Biology Laboratory at the University of Colorado Cancer Center. As such, the key personnel of this project possess considerable expertise in all the methods required for the successful completion of this award. These include flow cytometry, RNAseq, cell proliferation assays and cytokine microarray analysis. Dr. Hankinson has additionally built collaborative relationships with international leaders in ACP research. Most relevant to this award proposal is that with Dr. Juan Pedro Martinez-Barbera, who has established the only animal models of ACP. If the results of this work are promising, we will proceed to animal studies through collaboration with Dr. Martinez-Barbera. If the results do not indicate the potential for considerable advancement in the therapy for ACP, we will continue to focus our resources on the lines of research that were defined in our recent publication regarding ACP gene expression.

项目总结