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Abstract 3266: Inhibition of Rho-associated kinase 2 suppresses MYCN expression and induces differentiation of neuroblastoma
Conclusions: Our results show the significance of the non-canonical/PCP signaling cascade in neuroblastoma development and progression. Furthermore, ROCK inhibition suppress the growth of neuroblastoma in preclinical models and provide a novel option for improved treatment of high-risk neuroblastoma.Citation Format: Cecilia Dyberg, David Forsberg, Susanne Fransson, Jessika Lännerholm Palm, Bjorn Helge Haug, Baldur Sveinbjornsson, Tommy Martinsson, Per Kogner, John Inge Johnsen, Malin Wickstrom. Inhibition of Rho-associated kinase 2 suppresses MYCN expression and induces differentiation of neuroblastoma. [abstract]. In: Pr...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Dyberg, C., Forsberg, D., Fransson, S., Lannerholm Palm, J., Haug, B. H., Sveinbȷornsson, B., Martinsson, T., Kogner, P., Johnsen, J. I., Wickstrom, M. Tags: Tumor Biology Source Type: research

Abstract 475: Identification of SHANK2 as a tumor suppressor disrupted by recurrent somatic structural variation (SV) in neuroblastoma
Background. Neuroblastoma is a malignancy of the developing sympathetic nervous system which exacts significant morbidity and mortality in children. Large sequencing efforts have revealed a relative paucity of somatic point mutations in this and other childhood cancers. Structural variations (SVs) including translocations, inversions, deletions, duplications, and other complex events can occur in germline DNA or be acquired somatically in tumors. Recurrent somatic SVs affecting known genes are likely to be functional and may elucidate novel tumor suppressors or oncogenes.Methods. We are performing whole-genome sequencing (...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Conkrite, K., Ferraro, N., McDaniel, L., Oldridge, D. A., Attiyeh, E., Asgharzadeh, S., Diamond, M., Guidry Auvil, J., Davidsen, T., Smith, M., London, W. B., Seeger, R., Khan, J., Gerhard, D. S., Maris, J. M., Diskin, S. J. Tags: Tumor Biology Source Type: research

Abstract 191: The role of microRNAs in the epigenetic silencing of CHD5, a tumor suppressor in neuroblastoma
Background: Neuroblastoma (NB) is a tumor of the sympathetic nervous system that is the most common extracranial solid tumor of childhood. NBs show remarkable clinical heterogeneity, and we, along with others, have identified different patterns of genomic change that underlie these diverse clinical behaviors. We first identified 1p deletion as a characteristic change in advanced stage NBs. CHD5, a tumor suppressor gene, was first identified because of its location on 1p36. However, mutation of the remaining allele of CHD5 is rare in these tumors. Therefore, it is likely that epigenetic mechanisms play important roles in CH...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Naraparaju, K., Kolla, V., Zhuang, T., Higashi, M., Blobel, G. A., Brodeur, G. M. Tags: Molecular and Cellular Biology Source Type: research

Abstract 336: CD73 induces actin polymerization to protect epithelial cell-cell adhesions: Loss of this physiological reflex in endometrial carcinoma
We previously reported that ecto-5′nucleotidase (CD73)-generated adenosine prevents hypoxia-mediated breakdown of the epithelial barrier in normal endometrium in vivo and that CD73 is down-regulated in advanced stage endometrial carcinomas (EC). Loss of CD73 occurred specifically in the carcinoma cells. CD73-generated adenosine is heightened in tissues overwhelmed by inflammation, ischemia, or hypoxia. We hypothesized that the loss of CD73 in EC supports tumor progression by negating the reflex of extracellular adenosine to protect epithelial cell integrity. CD73 was associated with epithelial differentiation in vitro in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Bowser, J. L., Blackburn, M. R., Dunner, K., Broaddus, R. R. Tags: Tumor Biology Source Type: research

Abstract 3105: Neuropeptide Y Y5 receptor in neuroblastoma chemoresistance
Neuroblastoma (NB) is a pediatric tumor with heterogeneous phenotypes. While low stage tumors carry favorable prognosis, over 50% of high risk NB relapses after treatment with fatal outcome. Thus, developing therapies targeting this refractory form of NB remains an unsolved clinical problem. Neuropeptide Y (NPY) is a sympathetic neurotransmitter released from NB cells. High systemic levels of NPY are associated with poor clinical outcome of the disease, which is in agreement with its proliferative effect in NB cells and angiogenic properties. While all of the above functions of NPY are mediated mainly by its Y2 receptor (Y...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Trinh, E., Czarnecka, M., Hong, S.-H., Lu, C., Martin, S., Galli, S., Izycka-Swieszewska, E., Kuan-Celarier, A., Christian, D., Horton, M., Tilan, J. U., Kitlinska, J. B. Tags: Tumor Biology Source Type: research

Abstract 5423: Novel targeted therapy for neuroblastoma: Silencing the MXD3 gene using siRNA
Neuroblastoma is a cancer of the sympathetic nervous system and the most common extracranial solid tumor in children. Almost half of neuroblastoma patients have a high-risk phenotype at diagnosis: metastatic disease. Prognosis of these patients is very poor with only 30% survival despite the most intensive therapies currently available. In addition, patients who respond successfully to treatment suffer from side effects from chemo and radiation therapies, leading to life-long irreversible complications. Therefore, there is a desperate need for a neuroblastoma-targeted therapy that is more effective and has fewer side effec...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Duong, C., Chen, C., Yoshida, S., Barisone, G., Nolta, J., Diaz, E., Nitin, N., Satake, N. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research