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Pdx ewing sarcoma

Amanda Balboni Iniguez, Björn Stolte, Emily Jue Wang, Amy Saur Conway, Gabriela Alexe, Neekesh V Dharia, Nicholas Kwiatkowski, Tinghu Zhang, Brian J Abraham, Jaume Mora, Peter Kalev, Alan Leggett, Dipanjan Chowdhury, Cyril H Benes, Richard A Young, Nathanael S Gray, Kimberly Stegmaier
Many cancer types are driven by oncogenic transcription factors that have been difficult to drug. Transcriptional inhibitors, however, may offer inroads into targeting these cancers. Through chemical genomics screening, we identified that Ewing sarcoma is a disease with preferential sensitivity to THZ1, a covalent small-molecule CDK7/12/13 inhibitor. The selective CDK12/13 inhibitor, THZ531, impairs DNA damage repair in an EWS/FLI-dependent manner, supporting a synthetic lethal relationship between response to THZ1/THZ531 and EWS/FLI expression...
February 12, 2018: Cancer Cell
Jad El-Hoss, Duohui Jing, Kathryn Evans, Cara Toscan, Jinhan Xie, Hyunjoo Lee, Renea A Taylor, Mitchell G Lawrence, Gail P Risbridger, Karen L MacKenzie, Rosemary Sutton, Richard B Lock
Patient derived xenografts (PDXs) have become a vital, frequently used, component of anti-cancer drug development. PDXs can be serially passaged in vivo for years, and shared across laboratories. As a consequence, the potential for mis-identification and cross-contamination is possible, yet authentication of PDXs appears limited. We present a PDX Authentication System (PAS), by combining a commercially available OpenArray assay of single nucleotide polymorphisms (SNPs) with in-house R studio programs, to validate PDXs established in individual mice from acute lymphoblastic leukemia biopsies...
September 13, 2016: Oncotarget
Srikanth R Ambati, Jae-Hung Shieh, Benet Pera, Eloisi Caldas Lopes, Anisha Chaudhry, Elissa W P Wong, Ashish Saxena, Tsann-Long Su, Malcolm A S Moore
DNA damaging agents cause rapid shrinkage of tumors and form the basis of chemotherapy for sarcomas despite significant toxicities. Drugs having superior efficacy and wider therapeutic windows are needed to improve patient outcomes. We used cell proliferation and apoptosis assays in sarcoma cell lines and benign cells; γ-H2AX expression, comet assay, immunoblot analyses and drug combination studies in vitro and in patient derived xenograft (PDX) models. BO-1055 caused apoptosis and cell death in a concentration and time dependent manner in sarcoma cell lines...
July 12, 2016: Oncotarget
José Luis Ordóñez, Ana Teresa Amaral, Angel M Carcaboso, David Herrero-Martín, María del Carmen García-Macías, Vicky Sevillano, Diego Alonso, Guillem Pascual-Pasto, Laura San-Segundo, Monica Vila-Ubach, Telmo Rodrigues, Susana Fraile, Cristina Teodosio, Agustín Mayo-Iscar, Miguel Aracil, Carlos María Galmarini, Oscar M Tirado, Jaume Mora, Enrique de Álava
Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments...
August 7, 2015: Oncotarget
Tsuyoshi Chijiwa, Kenji Kawai, Akira Noguchi, Hidemitsu Sato, Akimune Hayashi, Haruhiko Cho, Manabu Shiozawa, Takeshi Kishida, Soichiro Morinaga, Tomoyuki Yokose, Makoto Katayama, Nobuo Takenaka, Hiroshi Suemizu, Roppei Yamada, Yoshiyasu Nakamura, Takashi Ohtsu, Yasuo Takano, Kohzoh Imai, Yohei Miyagi, Masato Nakamura
Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies...
July 2015: International Journal of Oncology
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