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Min Xie, Farhad Vesuna, Saritha Tantravedi, Guus M Bol, Marise R Heerma van Voss, Katriana Nugent, Reem Malek, Kathleen L Gabrielson, Paul J Van Diest, Phuoc T Tran, Venu Raman
Despite advances in diagnosis and treatment, prostate cancer is the most prevalent cancer in males and the second-highest cause of cancer-related mortality in men. We identified an RNA helicase gene, DDX3 (DDX3X), which is over-expressed in prostate cancers, and whose expression is directly correlated with high Gleason scores. Knockdown of DDX3 in aggressive prostate cancer cell lines DU145 and 22Rv1 resulted in significantly reduced clonogenicity. To target DDX3, we rationally designed a small molecule, RK-33, which docks into the ATP-binding domain of DDX3...
September 12, 2016: Cancer Research
B A Wilky, C Kim, G McCarty, E A Montgomery, K Kammers, L R DeVine, R N Cole, V Raman, D M Loeb
RNA helicase DDX3 has oncogenic activity in breast and lung cancers and is required for translation of complex mRNA transcripts, including those encoding key cell-cycle regulatory proteins. We sought to determine the expression and function of DDX3 in sarcoma cells, and to investigate the antitumor activity of a novel small molecule DDX3 inhibitor, RK-33. Utilizing various sarcoma cell lines, xenografts and human tissue microarrays, we measured DDX3 expression at the mRNA and protein levels, and evaluated cytotoxicity of RK-33 in sarcoma cell lines...
May 19, 2016: Oncogene
Guus Martinus Bol, Raheela Khan, Marise Rosa Heerma van Voss, Saritha Tantravedi, Dorian Korz, Yoshinori Kato, Venu Raman
BACKGROUND: The DDX3 helicase inhibitor RK-33 is a newly developed anticancer agent that showed promising results in preclinical research (Bol et al. EMBO Mol Med, 7(5):648-649, 2015). However, due to the physicochemical and pharmacological characteristics of RK-33, we initiated development of alternative formulations of RK-33 by preparing sustained release nanoparticles that can be administered intravenously. METHODS: In this study, RK-33 was encapsulated in poly(lactic-co-glycolic acid) (PLGA), one of the most well-developed biodegradable polymers, using the emulsion solvent evaporation method...
October 2015: Cancer Chemotherapy and Pharmacology
Marise R Heerma van Voss, Farhad Vesuna, Kari Trumpi, Justin Brilliant, Cynthia Berlinicke, Wendy de Leng, Onno Kranenburg, G Johan Offerhaus, Horst Bürger, Elsken van der Wall, Paul J van Diest, Venu Raman
Identifying druggable targets in the Wnt-signaling pathway can optimize colorectal cancer treatment. Recent studies have identified a member of the RNA helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells without activating mutations in the Wnt-signaling pathway. In this study, we evaluated whether DDX3 plays a role in the constitutively active Wnt pathway that drives colorectal cancer. We determined DDX3 expression levels in 303 colorectal cancers by immunohistochemistry. 39% of tumors overexpressed DDX3...
September 29, 2015: Oncotarget
Guus M Bol, Farhad Vesuna, Min Xie, Jing Zeng, Khaled Aziz, Nishant Gandhi, Anne Levine, Ashley Irving, Dorian Korz, Saritha Tantravedi, Marise R Heerma van Voss, Kathleen Gabrielson, Evan A Bordt, Brian M Polster, Leslie Cope, Petra van der Groep, Atul Kondaskar, Michelle A Rudek, Ramachandra S Hosmane, Elsken van der Wall, Paul J van Diest, Phuoc T Tran, Venu Raman
Lung cancer is the most common malignancy worldwide and is a focus for developing targeted therapies due to its refractory nature to current treatment. We identified a RNA helicase, DDX3, which is overexpressed in many cancer types including lung cancer and is associated with lower survival in lung cancer patients. We designed a first-in-class small molecule inhibitor, RK-33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK-33 caused G1 cell cycle arrest, induced apoptosis, and promoted radiation sensitization in DDX3-overexpressing cells...
May 2015: EMBO Molecular Medicine
W Rzeski, R Paduch, J Klatka, M Kandefer-Szerszeń, A Stepulak, P Pozarowski, B Zdzisińska
Two new cell lines, designated as RK-33 and RK-45, have been successfully established by an outgrowth technique from two different larynx tumours obtained from patients after laryngectomy. Both cell lineshave been maintained incultureforover 18 monthsandrecently have reached passage number 220 (RK-33) and 110 (RK-45). The cells display an epithelial morphology and multiply with a population doubling time of about 24 h (RK-33) and about 40 h (RK-45). The epithelial nature of the cells was also confirmed by expression of cytokeratins 8 and 18...
2002: Folia Histochemica et Cytobiologica
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