• Filter By:
• Specialty
• Source
• Condition
• Cancer
• Infectious Disease
• Drug
• Training
• Management
• Procedure
• Therapy
• Vaccine
• Nutrition
• Country

Role of HO-1-ROS-HDAC4-miR-206 Axis in RMS
Rhabdomyosarcoma (RMS) is an aggressive soft tissue cancer characterized by disturbed myogenic differentiation. Here we report a role for the oxidative stress response factor HO-1 in progression of RMS. We found that HO-1 was elevated and its effector target miR-206 decreased in RMS cell lines and clinical primary tumors of the more aggressive alveolar phenotype (aRMS). In embryonal RMS (eRMS), HO-1 expression was induced by Pax3/7-FoxO1, an aRMS hallmark oncogene, followed by a drop in miR-206 levels. Inhibition of HO-1 by tin protoporphyrin (SnPP) or siRNA downregulated Pax3/7-FoxO1 target genes and induced a myogenic pr...
Source: Cancer Research - October 1, 2016 Category: Cancer & Oncology Authors: Ciesla, M., Marona, P., Kozakowska, M., Jez, M., Seczynska, M., Loboda, A., Bukowska-Strakova, K., Szade, A., Walawender, M., Kusior, M., Stepniewski, J., Szade, K., Krist, B., Yagensky, O., Urbanik, A., Kazanowska, B., Dulak, J., Jozkowicz, A. Tags: Molecular and Cellular Pathobiology Source Type: research

Abstract PR10: The chromatin remodeler CHD4 as a potential specific target for alveolar rhabdomyosarcoma therapy
Fusion-positive alveolar rhabdomyosarcoma (FP-RMS) is a paediatric tumour driven by an oncogenic fusion transcription factor, PAX3-FOXO1. Conventional chemotherapy is only effective for low risk patients which carry no metastasis, achieving a 5-year overall survival of 65%. The unique presence of this fusion protein in FP-RMS as well as the tumour cell survival dependency on PAX3-FOXO1 make this transcription factor a promising target for therapy. However, due to the difficulties associated with drug development targeting transcription factors, we performed a combined proteomic and genetic screen to identify new druggable ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Marques, J., Boehm, M., Wachtel, M., Schaefer, B. Tags: Epigenetics Source Type: research

Abstract 487: Whole genome screen to identify genes targeting MYCN-driven embryonal tumors
MYCN is a driver of neuroblastoma (NB) tumorigenesis and is over-expressed in a number of tumors of embryonal origin, including rhabdomyosarcoma, medulloblastoma and diffuse intrinsic pontine gliomas. We sought to identify regulators of MYCN transcription by performing a whole genome screen (WGS) for regulators of MYCN promoter activity using a NB cell model. A plasmid containing the MYCN promoter (1.3kb upstream of MYCN TSS) fused to luciferase and stably integrated into the genome of NGP NB cells was the readout system. NGP-MYCNpluc, was selected based on MYCN luciferase activity inhibition by ATRA and HDAC inhibitors to...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Thiele, C. J., Liu, Z., Veschi, V., Buehler, E., Martin, S. Tags: Tumor Biology Source Type: research

Abstract 3792: SKP2 supports cell proliferation and is regulated by Notch signaling in myoblasts and embryonal rhabdomyosarcoma
Conclusion:Altogether, these preliminary experiments suggest that SKP2 could be regulated by Notch signaling in ERMS and that its inhibition hampers tumor cell proliferative capability.Note: This abstract was not presented at the meeting.Citation Format: Rossella Rota, Laura Adesso, Beatrice Conti, Roberta Ciarapica, Lavinia Raimondi, Maria De Salvo, Sonia Rodriguez, Nadia Carlesso, Lucio Miele, Franco Locatelli. SKP2 supports cell proliferation and is regulated by Notch signaling in myoblasts and embryonal rhabdomyosarcoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Rese...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rota, R., Adesso, L., Conti, B., Ciarapica, R., De Raimondi, L., Salvo, M., Rodriguez, S., Carlesso, N., Miele, L., Locatelli, F. Tags: Molecular and Cellular Biology Source Type: research

Targeting of PAX3-FOXO1 by PLK1 Inhibition
In this report, we addressed this challenge by developing a two-armed screen for druggable upstream regulatory kinases in the PAX3/7-FOXO1 pathway. Screening libraries of kinome siRNA and small molecules, we defined PLK1 as an upstream-acting regulator. Mechanistically, PLK1 interacted with and phosphorylated PAX3-FOXO1 at the novel site S503, leading to protein stabilization. Notably, PLK1 inhibition led to elevated ubiquitination and rapid proteasomal degradation of the PAX3-FOXO1 chimeric oncoprotein. On this basis, we embarked on a preclinical validation of PLK1 as a target in a xenograft mouse model of aRMS, where the...
Source: Cancer Research - January 4, 2015 Category: Cancer & Oncology Authors: Thalhammer, V., Lopez–Garcia, L. A., Herrero–Martin, D., Hecker, R., Laubscher, D., Gierisch, M. E., Wachtel, M., Bode, P., Nanni, P., Blank, B., Koscielniak, E., Schafer, B. W. Tags: Molecular and Cellular Pathobiology Source Type: research

Abstract PR02: Negative regulation of myogenesis by Mtor: A pathway toward differentiation therapy in rhabdomyosarcoma
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, is composed of skeletal myoblast-like cells that have lost the capacity to terminally differentiate. This suggests that RMS cells may contain a factor that blocks normal muscle differentiation. Because cell cycle arrest is coupled to muscle differentiation, identifying putative negative regulators of differentiation could lead to novel therapeutic approaches aimed at fostering terminal differentiation. To gain insight into the events that normally trigger the initial phase of muscle differentiation, we carried out a high content cell-based screen usin...
Source: Cancer Research - October 9, 2014 Category: Cancer & Oncology Authors: Wilson, R. A., Liu, J., Xu, L., Zheng, Y., Skapek, S. X. Tags: Developmental Biology of Pediatric Malignancies Source Type: research

Abstract 3422: RNAi screening identifies FGFR4 as a modulator of growth and survival in Ewing sarcoma
Ewing sarcoma is the second most common cancer of bone and soft tissue arising in children and young adults. Standard treatment of Ewing sarcoma includes surgery, radiation, and chemotherapy largely consisting of combinations of non-targeted cytotoxic agents. Although the survival rate has improved for patients treated for localized disease, the survival rate of patients with metastatic tumor remains lower than 30%. In order to improve therapeutic options for Ewing Sarcoma, we employed a functional genomics approach based on RNA interference (RNAi) screening to identify genes whose silencing affected the proliferation and ...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Azorsa, D. O., Gonzales, I. M., Arora, S., Hagelstrom, R. T., Little, T. H., Arceci, R. J., Mousses, S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 3966: PLK1 regulates PAX3-FOXO1 stability and its inhibition mediates regression of alveolar rhabdomyosarcoma xenograft tumors
Oncogenic addiction provides an opportunity to develop new treatment options, especially for childhood cancers. Pediatric tumors contain a lower number of oncogenic mutations compared to most adult cancers, suggesting stronger dependency on individual oncogenes, such as chimeric transcription factors that have the ability to control multiple oncogenic pathways. Taking advantage of this addiction, targeting of oncogenic transcription factors becomes a new powerful strategy for therapy of translocation positive pediatric tumors like alveolar rhabdomyosarcoma (aRMS), which is characterized by a very dismal prognosis. As trans...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Thalhammer, V., Herrero–Martin, D., Hecker, R., Laubscher, D., Lopez–Garcia, L., Wachtel, M., Bode, P., Schafer, B. Tags: Tumor Biology Source Type: research

Abstract 764: A role for GLI1 in the development of multidrug resistance in rhabdomyosarcoma (RMS) cells
RMS is the most common sarcoma of childhood. About 30% of patients with localized tumors will recur following treatment. The outcome for patients with recurrent RMS remains poor. Therefore, development of chemotherapy resistance during RMS therapy represents an important problem and novel approaches to prevent or reverse drug resistance are essential. Activation of multidrug transporter genes, including MDR1, MRP1, LRP and TAP1 represents an important mechanism for drug resistance in RMS. However, the mechanism of expression of multidrug resistance genes in RMS is incompletely understood. Recent reports have suggested a ro...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Yoon, J. W., Lamm, M., Leong, K.-F., Iannaccone, S., Iannaccone, P., Walterhouse, D. Tags: Experimental and Molecular Therapeutics Source Type: research