ZM447439, a Novel Promising Aurora Kinase Inhibitor, Provokes Antiproliferative and Proapoptotic Effects Alone and in Combination with Bio- and Chemotherapeutic Agents in Gastroenteropancreatic Neuroendocrine Tumor Cell Lines

2010 ◽  
Vol 91 (2) ◽  
pp. 121-130 ◽  
Author(s):  
I. Georgieva ◽  
D. Koychev ◽  
Y. Wang ◽  
J. Holstein ◽  
W. Hopfenmüller ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Neuroendocrine Tumor ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Chemotherapeutic Agents ◽  
Tumor Cell Lines ◽  
Aurora Kinase Inhibitor ◽  
Gastroenteropancreatic Neuroendocrine Tumor

scholarly journals Preclinical Evaluation of AMG 900, a Novel Potent and Highly Selective Pan-Aurora Kinase Inhibitor with Activity in Taxane-Resistant Tumor Cell Lines

2010 ◽  
Vol 70 (23) ◽  
pp. 9846-9854 ◽  
Author(s):  
Marc Payton ◽  
Tammy L. Bush ◽  
Grace Chung ◽  
Beth Ziegler ◽  
Patrick Eden ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Tumor Cell Lines ◽  
Aurora Kinase Inhibitor ◽  
Preclinical Evaluation

scholarly journals Pan Aurora Kinase Inhibitor: A Promising Targeted-Therapy in Dedifferentiated Liposarcomas With Differential Efficiency Depending on Sarcoma Molecular Profile

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 583 ◽  
Author(s):  
Jean Camille Mattei ◽  
Corinne Bouvier-Labit ◽  
Doriane Barets ◽  
Nicolas Macagno ◽  
Mathieu Chocry ◽  
...  
Keyword(s):  
Cell Lines ◽  
Standard Treatment ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Molecular Profile ◽  
Molecular Characteristics ◽  
Aurora Kinase Inhibitor ◽  
Free Survival ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60–70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS.

Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cell lines characterized for EGFR expression and K-ras mutation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14583-e14583 ◽  
Author(s):  
J. Barriere ◽  
J. Fischel ◽  
P. Formento ◽  
N. Renée ◽  
M. Francoual ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Human Cancer ◽  
Tumor Cell Lines ◽  
Ras Mutation ◽  
Egfr Expression ◽  
Mutational Status

e14583 Background: Mutated K-ras protein is a strong predictive factor of cetuximab resistance, bypassing the classical direct inhibitory effect on epidermal growth factor receptor (EGFR) signaling. However, cetuximab is also able to mediate ADCC, which may be part of the clinical response. The aim of this ex-vivo study was to quantify cetuximab-mediated ADCC on various human cancer cell lines characterized for EGFR-expression and K-ras mutation. Methods: Two K-ras mutated cell lines over-expressing EGFR and resistant to anti-EGFR tyrosine kinase inhibitor were tested (Capan-1 and Capan-2, pancreatic), along with 2 K-ras wild-type cell lines over- expressing EGFR (CAL166, head and neck; A431, epidermoid carcinoma) and an EGFR-negative cell line (OCM1, uveal melanoma). The tested monoclonal antibodies (mAbs) were: cetuximab (Merck, anti-EGFR IgG1 mAb), panitumumab (Amgen, anti-EGFR IgG2 mAb), and as a negative control, rituximab (Roche, IgG1 anti-CD20 mAb). ADCC (51Cr release assay) was performed using freshly- isolated peripheral blood mononuclear cells from a healthy donor. Results were expressed as % of potentially maximum 51Cr release. Results: Cetuximab mediates ADCC against EGFR-over-expressing cell lines CAL166 (38.4 ± 3.1 %), A431 (13.5 ± 1.7 %), Capan-1 (31.2 ± 0.8 %) and Capan-2 (27.8 ± 8.6 %) irrespective of the K-ras mutational status, but not against EGFR-negative OCM-1 (6.2 ± 1 %). Conversely, unlike IgG1 cetuximab, the anti-EGFR IgG2 panitumumab and the irrelevant antibody rituximab were both unable to induce significant ADCC (< 10 % on all tested cell lines). Conclusions: Cetuximab-mediated ADCC is independent of the K-ras mutational status of the tumor cell lines. Present data suggest that cetuximab may remain of clinical interest in K-ras-mutated patients. Immunostimulation, as well as new generation anti-EGFR mAbs with improved ability to induce ADCC, may be promising in the management of K-ras-mutated patients. No significant financial relationships to disclose.

275 The effect of Aurora kinase inhibitor, ZM447439, on human mammary eptihelial cell lines with BRCA2 mutation

2010 ◽  
Vol 8 (5) ◽  
pp. 72
Author(s):  
L. Vidarsdottir ◽  
A.M. Halldorsdottir ◽  
G. Steingrimsdottir ◽  
S.K. Bodvarsdottir ◽  
H.M. Ogmundsdottir ◽  
...  
Keyword(s):  
Cell Lines ◽  
Kinase Inhibitor ◽  
Brca2 Mutation ◽  
Aurora Kinase ◽  
Aurora Kinase Inhibitor

scholarly journals A water soluble tri-cationic porphyrin–EDTA conjugate induces apoptosis in human neuroendocrine tumor cell lines

2012 ◽  
Vol 40 ◽  
pp. 108-113 ◽  
Author(s):  
Gert Schwach ◽  
Patchanita Thamyongkit ◽  
Lorenz Michael Reith ◽  
Bernhard Svejda ◽  
Günther Knör ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Neuroendocrine Tumor ◽  
Cell Lines ◽  
Water Soluble ◽  
Tumor Cell Lines ◽  
Cationic Porphyrin
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