Journal: Journal of biomedical materials research. Part A

Article Title: Heparin-collagen I bilayers stimulate FAK/ERK½ signaling via α2β1 integrin to support the growth and anti-inflammatory potency of mesenchymal stromal cells.

doi: 10.1002/jbm.a.37614

Figure Lengend Snippet: FIGURE 7 FAK-ERK½ levels are not affected by αvβ3 inhibition. FAK and ERK½ protein bands from (A) donor BMSC 182 and (B) BMSC 271 in response to Cilengitide treatment. (C–F) Plotted protein intensity band levels of total and phosphorylated FAK (C, D) and ERK½ (E, F) for two MSC donors treated with Cilengitide for 24 h.

Article Snippet: BTT-3033 (4027, TOCRIS, place) and Cilengitide (SML1594-5MG, Sigma Aldrich), are selective inhibitors against α2β1 and αvβ3 integrins, respectively.

Techniques: Inhibition

Journal: Journal of biomedical materials research. Part A

Article Title: Heparin-collagen I bilayers stimulate FAK/ERK½ signaling via α2β1 integrin to support the growth and anti-inflammatory potency of mesenchymal stromal cells.

doi: 10.1002/jbm.a.37614

Figure Lengend Snippet: FIGURE 8 Integrin α2β1 supports MSCs viability on HEP/COL substrates. (A) Drug–response curves for MSCs (two donors) viability upon stimulation with incremental dosages of BTT-3033, Cilengitide, and SCH772984 on HEP/COL multilayers. Data were normalized between 0 and 100 and fitted by non-linear regression to identify specific IC50 and IC75 dosages. n = 3. (B) Fold change for Annexin V positive cells (donors BMSC 182 and 271) upon treatment with computed IC75s for BTT-3033, Cilengitide, and SCH772984. Data represented the mean ± SEM of n = 6. Two-way ANOVA was used for statistical analysis. (*) Significantly different than vehicle; *p ≤.05; **p ≤.01; ***p ≤.001 (#) Marginally significant .05 < p ≤.1. (C) Representative images of apoptotic cells cultured on HEP/COL with and without drug stimulations, scale bar 100 μm.

Article Snippet: BTT-3033 (4027, TOCRIS, place) and Cilengitide (SML1594-5MG, Sigma Aldrich), are selective inhibitors against α2β1 and αvβ3 integrins, respectively.

Techniques: Cell Culture

Journal: Journal of the American Chemical Society

Article Title: A Chemically Cross-Linked Knottin Dimer Binds Integrins with Picomolar Affinity and Inhibits Tumor Cell Migration and Proliferation

doi: 10.1021/ja508416e

Figure Lengend Snippet: Figure 1. Binding assays. Competition binding of Alexa488-2.5F monomer to integrin receptors expressed on U87MG cells (A) and MDA-MB-231 cells (B) by knottin monomer, dimers, and Cilengitide, as measured by

Article Snippet: 2 × 104 cells were incubated with varying concentrations of knottins or Cilengitide (BOC Sciences) and a constant concentration of competitor for 10 h at 4 °C (Supporting Information).

Techniques: Binding Assay

Journal: Journal of the American Chemical Society

Article Title: A Chemically Cross-Linked Knottin Dimer Binds Integrins with Picomolar Affinity and Inhibits Tumor Cell Migration and Proliferation

doi: 10.1021/ja508416e

Figure Lengend Snippet: Figure 2. Effect of D2.5F_1 dimer (red), 2.5F monomer (blue), or Cilengitide (green) on U87MG cell migration compared to untreated control (brown). (A) Bright field images showing tumor cell migration into

Article Snippet: 2 × 104 cells were incubated with varying concentrations of knottins or Cilengitide (BOC Sciences) and a constant concentration of competitor for 10 h at 4 °C (Supporting Information).

Techniques: Migration, Control

Journal: Journal of the American Chemical Society

Article Title: A Chemically Cross-Linked Knottin Dimer Binds Integrins with Picomolar Affinity and Inhibits Tumor Cell Migration and Proliferation

doi: 10.1021/ja508416e

Figure Lengend Snippet: Figure 3. Effect of D2.5F_1 dimer (red), 2.5F monomer (blue), or Cilengitide (green) on MDA-MB-231 cell

Article Snippet: 2 × 104 cells were incubated with varying concentrations of knottins or Cilengitide (BOC Sciences) and a constant concentration of competitor for 10 h at 4 °C (Supporting Information).

Techniques:

Journal: Clinical and Translational Medicine

Article Title: Inhibition of TGFβ1 activation prevents radiation‐induced lung fibrosis

doi: 10.1002/ctm2.1546

Figure Lengend Snippet: Cilengitide protected mice from radiation‐induced mortality. (A) The experimental time course starting at the time of irradiation is shown. Cilengitide was administered to the mice for 8 weeks beginning on the day the mice received 16 Gy of radiation to the thorax. The two control groups were not irradiated and received PBS or 15 mg/kg cilengitide. The other three groups were irradiated and left untreated or treated with 15 or 75 mg/kg cilengitide. (B) Photograph of mice after radiation exposure. (C) Photograph of mice at 24 weeks after irradiation. (D) Kaplan‒Meier survival curves starting at the time of irradiation were generated for 35 mice per group, and the mice sacrificed for histological examination were censored. (E) Mouse bodyweight was recorded as a general measure of health. Bars represent the means ± SEMs.

Article Snippet: Cilengitide was purchased from GL Biochem.

Techniques: Irradiation, Generated

Journal: Clinical and Translational Medicine

Article Title: Inhibition of TGFβ1 activation prevents radiation‐induced lung fibrosis

doi: 10.1002/ctm2.1546

Figure Lengend Snippet: Cilengitide prevented pulmonary tissue remodelling after irradiation in mice. (A) Haematoxylin–eosin (H&E)‐ and Masson's trichrome‐stained sections from mice in each group at 16 and 20 weeks after irradiation. (B) Assessment of the severity of pulmonary fibrosis via the modified Ashcroft score. (C) Hydroxyproline content in mouse lung homogenates from mice that received irradiation and/or cilengitide at Week 20 after irradiation. (D) Average thickness of the mouse pulmonary septa after irradiation and treatment with 15 or 75 mg/kg cilengitide. (E) Real‐time qPCR analysis of Col1a1 mRNA expression in the right lung tissue of irradiated and/or cilengitide‐treated mice. Bars represent the means ± SEMs (* p < .05; ** p < .01; *** p < .001).

Article Snippet: Cilengitide was purchased from GL Biochem.

Techniques: Irradiation, Staining, Modification, Expressing

Journal: Clinical and Translational Medicine

Article Title: Inhibition of TGFβ1 activation prevents radiation‐induced lung fibrosis

doi: 10.1002/ctm2.1546

Figure Lengend Snippet: Cilengitide prevented the activation of latent TGFβ1. (A and B) Total and active TGFβ1 levels in the serum of the placebo‐ or cilengitide‐treated mice after irradiation or the sham irradiation procedure were determined by ELISAs. (C) Western blot analysis of integrin αv, collagen and α‐SMA protein levels in the PBS‐ or cilengitide‐treated MRC‐5 cells that received irradiation or underwent the sham irradiation procedure. (D) Total and active TGFβ1 levels in the supernatants of the PBS‐ or cilengitide‐treated MRC‐5 cells that received 8 Gy radiation or underwent the sham irradiation procedure. (E) Western blot analysis of Smad2/3 and p‐Smad2/3 protein levels in the PBS‐ or cilengitide‐treated MRC‐5 cells that received 8 Gy radiation or underwent the sham irradiation procedure. (F) A dual‐luciferase assay was performed to detect TGFβ1 activity. (G) Real‐time qPCR analysis of Acta2 and Col1a1 mRNA expression in irradiated MRC‐5 cells treated with exogenous latent TGFβ1 or active TGFβ1 and PBS or cilengitide.

Article Snippet: Cilengitide was purchased from GL Biochem.

Techniques: Activation Assay, Irradiation, Western Blot, Luciferase, Activity Assay, Expressing

Journal: Clinical and Translational Medicine

Article Title: Inhibition of TGFβ1 activation prevents radiation‐induced lung fibrosis

doi: 10.1002/ctm2.1546

Figure Lengend Snippet: Schematic of the working model of integrin‐mediated TGFβ1 activation in myofibroblasts. (A) Activated TGFβ1 has a superior capacity in predicting radiation pneumonitis (RP) risk, and plays a vital role in the development of radiation‐induced pulmonary fibrosis (RIPF). (B) Conditional knock out Itgav in myofibroblasts prevented mice from developing RIPF. (C) Cilengitide alleviated the development of RIPF by inhibiting αv integrin‐mediated TGFβ1 activation and may be used in targeted approaches for preventing RIPF.

Article Snippet: Cilengitide was purchased from GL Biochem.

Techniques: Activation Assay, Knock-Out