Journal: Journal of cellular physiology

Article Title: Blocking Fibrotic Signaling In Fibroblasts from Patients with Carpal Tunnel Syndrome

doi: 10.1002/jcp.25901

Figure Lengend Snippet: Gene expression analysis using qRT-PCR of known CTS fibrosis marker genes Col1, 3, CTGF, SERPINE1 upon cytokine receptor level inhibition. CTS fibroblasts were treated with TGF-β1 and TβRI (SD208), PDGFR (AG1296), EGFR (Lapatinib) and VEGFR (Axitinib) inhibitor for 24 hours. Gene expression is normalized to vehicle control. All data are expressed as mean ± SE. n=5. (* indicates p < 0.05, # indicates p < 0.01).

Article Snippet: Lapatinib (IC50: 10.8 nM) (Selleck Chemical, Houston, TX, S1028) is a small molecule kinase inhibitor that targets both EGFR1 and 2 (Her2) ( Moy et al., 2007 ).

Techniques: Gene Expression, Quantitative RT-PCR, Marker, Inhibition, Control

Journal: Journal of cellular physiology

Article Title: Blocking Fibrotic Signaling In Fibroblasts from Patients with Carpal Tunnel Syndrome

doi: 10.1002/jcp.25901

Figure Lengend Snippet: Smad reporter activity comparing cytokine receptor inhibition. Comparison of CTS fibroblasts treated with TGF-β1 and TβRI (SD208), PDGFR (AG1296), EGFR (Lapatinib) and VEGFR (Axitinib) inhibitor for 24 hours. Data are expressed as relative fold change from vehicle control. All data are expressed as mean ± SE. n=3. (# indicates p < 0.01).

Article Snippet: Lapatinib (IC50: 10.8 nM) (Selleck Chemical, Houston, TX, S1028) is a small molecule kinase inhibitor that targets both EGFR1 and 2 (Her2) ( Moy et al., 2007 ).

Techniques: Activity Assay, Inhibition, Comparison, Control

Journal: Scientific Reports

Article Title: Mesenchymal Stem Cells Exploit Extracellular Matrix as Mechanotransducer

doi: 10.1038/srep02425

Figure Lengend Snippet: (a) hMSCs cultured on single Fn fibers in osteogenic induction medium for 7 days with or without constant exposure to function-blocking antibodies. Percentage of ALP positive hMSCs is shown in the presence of function-blocking antibodies against integrin α5β1 (red), integrin αvβ3 (blue) or without antibodies (yellow). (b) Percentage of ALP positive hMSCs when cultured for 7 days on single Fn fibers in the presence (green) or absence (yellow) of the EGFR inhibitor GW572016 in osteogenic induction medium is shown. Data shown in a and b represent mean ± s.d. (n = 5). Asterisk p < 0.05 versus no antibody treatment (P = 0.0385 for α5β1 in (a)). Two asterisks: p < 0.01 versus no antibody treatment (P = 0.0038 for αvβ3 in (a)) or no drug treatment (p = 0.0092 for (b)).

Article Snippet: To block the activity of ErbB receptors, hMSCs (50 × 10 3 cells/ml) were allowed to attach for 1 hour on single Fn fibers in growth medium supplemented with GW572016 (1 μM, Lapatinib, Axon Medchem), and were subsequently cultured for 7 days in osteogenic induction medium supplemented with GW572016.

Techniques: Cell Culture, Blocking Assay

Journal: Disease Markers

Article Title: Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host

doi: 10.1155/2017/7849108

Figure Lengend Snippet: Anti-HER2 therapies and their immunostimulatory properties. The monoclonal antibodies trastuzumab and pertuzumab, in addition to inhibiting intracellular signaling downstream of HER2 activation (i.e., homo/heterodimerization and proteolytic cleavage of the HER2 extracellular domain), induce an antitumor immune response in the tumor microenvironment. Trastuzumab and pertuzumab bind to the extracellular domain of HER2 and, through their Fc portions, engage antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP) in Fc receptor-positive innate immune cells (i.e., NK lymphocytes, macrophages, monocytes, and neutrophils). Immune complex and opsonized tumor fragments are recognized and taken up by dendritic cells via the Fc receptor. Dendritic cells and other antigen-presenting cells (e.g., macrophages) present tumor antigens through MHC-II molecules to CD4+ T-helper lymphocytes, which release interferon- γ (IFN γ ), interleukin 2 (IL2), and IL21 to enhance the cytotoxic T cell response. Antigens presented by MHC-I molecules directly stimulate CD8+ cytotoxic T lymphocytes. CD8+ T cells can also recognize tumor antigens presented on MHC-I molecules by cancer cells themselves and initiate a cytotoxic response. Tyrosine kinase inhibitors (TKIs) (lapatinib and neratinib) block the kinase domain activity of HERs, disrupting the oncogenic signals that lead to proliferation, migration, invasion, and survival of cancer cells. In contrast to neratinib, lapatinib, in addition to blocking the TK domain of HER2 and HER1, affects the accumulation of HER2 on the surface of BC cells, leading to an increase in ADCC when combined with trastuzumab.

Article Snippet: Lapatinib (GW572016, Tyverb/Tykerb; Novartis, Switzerland) reversibly inhibits the intracellular tyrosine kinase domains of EGFR and HER2, inducing cell cycle arrest and apoptosis in BC cell lines through the cleavage of PARP and the activation of caspase 3 [ ].

Techniques: Bioprocessing, Activation Assay, Blocking Assay, Activity Assay, Migration

Journal: Disease Markers

Article Title: Predicting the Efficacy of HER2-Targeted Therapies: A Look at the Host

doi: 10.1155/2017/7849108

Figure Lengend Snippet: Evaluation of HER2-addiction and immune biomarkers in randomized trials investigating anti-HER2 targeted therapies.

Article Snippet: Lapatinib (GW572016, Tyverb/Tykerb; Novartis, Switzerland) reversibly inhibits the intracellular tyrosine kinase domains of EGFR and HER2, inducing cell cycle arrest and apoptosis in BC cell lines through the cleavage of PARP and the activation of caspase 3 [ ].

Techniques: Polymerase Chain Reaction, Adjuvant