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docetaxel-induced polyploidy

Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
April 25, 2017: British Journal of Cancer
Danielle C Chinn, William S Holland, Philip C Mack
PURPOSE: Aurora kinases are key regulators of mitotic events. Dysfunction of these kinases can cause polyploidy and chromosomal instability, a contributor to tumorigenesis. MK-5108 is a potent inhibitor of Aurora A kinase that has shown preclinical potent activity in malignancies of breast, cervical, colon, ovarian, and pancreatic origin. We sought to assess the preclinical efficacy of MK-5108 in a panel of non-small-cell lung cancer cell lines as a single agent and in combination with cisplatin and docetaxel...
July 2014: Journal of Cancer Research and Clinical Oncology
Tammy L Bush, Marc Payton, Scott Heller, Grace Chung, Kelly Hanestad, James B Rottman, Robert Loberg, Gregory Friberg, Richard L Kendall, Douglas Saffran, Robert Radinsky
Breast cancer is the most prevalent malignancy affecting women and ranks second in cancer-related deaths, in which death occurs primarily from metastatic disease. Triple-negative breast cancer (TNBC) is a more aggressive and metastatic subtype of breast cancer that is initially responsive to treatment of microtubule-targeting agents (MTA) such as taxanes. Recently, we reported the characterization of AMG 900, an orally bioavailable, potent, and highly selective pan-Aurora kinase inhibitor that is active in multidrug-resistant cell lines...
November 2013: Molecular Cancer Therapeutics
Juan Hao, Bi-bo Yuan, Yuan-fu Xu, Juan Yu, Guo-yan Liu, De-hua Wang
OBJECTIVE: To investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism. METHODS: Nocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay...
June 2012: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
Wenqing Qi, Laurence S Cooke, Xiaobing Liu, Lisa Rimsza, Denise J Roe, Ann Manziolli, Daniel O Persky, Thomas P Miller, Daruka Mahadevan
Auroras (A and B) are oncogenic serine/threonine kinases that play key roles in the mitotic phase of the eukaryotic cell cycle. Analysis of the leukemia lymphoma molecular profiling project (LLMPP) database indicates Aurora over-expression correlates with poor prognosis. A tissue microarray (TMA) composed of 20 paired mantle cell lymphoma (MCL) patients demonstrated >75% of patients had high levels Aurora expression. Aurora A and B were also found elevated in 13 aggressive B-NHL cell lines. MLN8237, an Aurora inhibitor induced G2/M arrest with polyploidy and abrogated Aurora A and histone-H3 phosphorylation...
April 1, 2011: Biochemical Pharmacology
Carolyn Wiltshire, Babloo L Singh, Jacqueline Stockley, Janis Fleming, Brendan Doyle, Robert Barnetson, Craig N Robson, Frank Kozielski, Hing Y Leung
Castrate-resistant prostate cancer remains a major clinical challenge. Due to the toxicity profile of taxane-based chemotherapy and treatment failure in some patients, novel agents with improved efficacy to side effect profiles are urgently needed. Eg5, a member of the kinesin-5 family, controls the formation of the bipolar spindle during cell division, and suppressed Eg5 function leads to mitotic arrest. S-Trityl-L-cysteine (STLC) is a novel Eg5-specific small-molecule inhibitor. Here, we report the first study to evaluate its use in prostate cancer...
June 2010: Molecular Cancer Therapeutics
H L Lin, T Y Liu, G Y Chau, W Y Lui, C W Chi
BACKGROUND: Previously, the authors observed that paclitaxel treatment of hepatoma cells resulted in differential cytotoxicity. Whether other antimicrotubule agents (docetaxel and 2-methoxyestradiol) are more effective than paclitaxel is not clear. Moreover, whether the modulation of reactive oxygen species (ROS) is involved in the drug-induced growth inhibition of hepatoma cells is not known. METHODS: The authors examined the effects of 2-methoxyestradiol, paclitaxel, and docetaxel on HepG2, Hep3B, HA22T/VGH, and Hepa1-6 hepatoma cell lines...
September 1, 2000: Cancer
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