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1	Usefulness of delE746-A750 and L858R Mutation-Specific Antibodies of EGFR for Predicting Treatment Outcome of Tyrosine Kinase Inhibitors Tang, En-kuei 24 July 2012 (has links) Efficacy of tyrosine kinase inhibitor (TKI) therapy depends on epidermal growth factor receptor (EGFR) mutation status in patients with non-small cell lung cancer (NSCLC). There has been an increasing interest in studying mutation-specific rabbit monoclonal antibodies of delE746-A750 mutation in exon 19 and L858R point mutation in exon 21 for detecting EGFR mutants. These two mutations account for approximately 90% of all EGFR mutations. We evaluated the two mutation-specific monoclonal antibodies for the detection of EGFR mutations by immunohistochemistry (IHC) and the relationship with treatment outcome and survival. Twenty-five patients (58.1%) harbored EGFR mutations. These mutations include delE746-A750 mutation for seven patients, L858R point mutation for in eighteen patients. IHC showed, for the delE746-A750 and L858R mutations, sensitivity (57.1% and 66.7%), specificity (97.3% and 100%), positive predictive value (80.0% and 100%), and negative predictive value (94.7% and 80.6%). Analysis for progression-free survival was not correlated to IHC staining, but the overall survival was correlated to IHC staining. These mutation-specific antibodies for delE746-A750 and L858R mutations have high positive predictive value and specificity for predefined EGFR mutations and may be suitable for screening for these predefined mutations. However, negative IHC results required further mutation analyses before excluding EGFR TKI therapy. L858R mutation-specific antibody tyrosine kinase inhibitor EGFR gene mutation delE746-A750
2	The effects of various combinations of different classes of anticancer drugs and tyrosine kinase inhibitors on the human MCF-7 breast carcinoma cell line Abrahams, Beynon January 2014 (has links) Magister Scientiae (Medical Bioscience) - MSc(MBS) / This study investigated the effects of TKIs on the growth and proliferation of MCF-7 breast carcinoma cells in culture. MCF-7 cells were exposed to different concentrations of TKIs alone and in combination with each other. Inhibition of cell growth by TKIs used individually occurred in a dose- and time-dependent manner. When EGFR Inhibitor I, EGFR Inhibitor II/BIBX1382 and the multi-specific EGFR/ErbB-2/ErB-4 Inhibitor were used in combination with each other at equimolar log dose concentrations, the combined effects on cell growth was significantly different to inhibitors used individually as reflected in a decreased EC50 (IC50) during combination treatments. Generally, for the combinations with DOX, CPL and the TKIs, synergistic as well as antagonistic effects were observed at isoeffective concentrations with resultant decreases in dose reduction indices (DRIs) implying greater efficacies with the respective combinations. In this study, conventional PCR was used to detect and illustrate the presence of the EGFR gene in the samples, while RT-qPCR was used to determine the mRNA expression levels of this gene in MCF-7 breast carcinoma cells Breast cancer Human MCF-7 breast carcinoma cells Epidermal growth factor receptor Tyrosine kinase inhibitors Doxorubicin Cisplatin EGFR inhibitor I EGFR inhibitor II/BIBX1382 EGFR/ErbB2/ErbB4 inhibitor Dose-response curves IC50/EC50 Drug combination analysis Synergism Antagonism Dose-reduction indices Haematoxylin and eosin staining Annexin V-Cy3 fluorescent staining Apoptosis EGFR gene expression analysis Real-time qPCR

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Usefulness of delE746-A750 and L858R Mutation-Specific Antibodies of EGFR for Predicting Treatment Outcome of Tyrosine Kinase Inhibitors

The effects of various combinations of different classes of anticancer drugs and tyrosine kinase inhibitors on the human MCF-7 breast carcinoma cell line