Journal: Frontiers in Oncology

Article Title: Activin A Signaling Regulates IL13Rα2 Expression to Promote Breast Cancer Metastasis

doi: 10.3389/fonc.2019.00032

Figure Lengend Snippet: INHBA is correlated with IL13Rα2 expression in breast cancer cells. (A) MII cells were cultured in DMEMF/12 medium containing 0.2% horse serum (HS) overnight and then treated with 10 ng/ml Activin A for different time points. Western blotting was performed using whole cell lysates to assess phosphorylation of Smad2 (Ser465/467), Smad3 (Ser423/425), Akt (Ser 473), and Erk1/2 (Thr202/Tyr204). Detection of total Smad2, Smad3, Akt, and Erk1/2 was used as loading controls. Protein expression was quantified using ImageJ software. (B) MII cells were mock-treated (DMSO) or treated 1 μM EW-7197 or SB-505124, in the presence or absence of 10 ng/ml Activin A for 1 h. Western blotting was performed using whole cell lysates to assess the phosphorylation status of Smad2 and Smad3. Total Smad2, Smad3, and β-actin were detected as loading controls. (C) MIV cells were treated with 1 μM EW-7197 or 1μM SB-505124 for 24 h. Real time qPCR was used to measure the mRNA expression of IL13Rα2. Asterisk ( * ) indicates a statistically significant difference between Activin A-treated and mock-treated cells ( n = 6; p < 0.05). (D) MIV cells were stably transduced with lentiviral vectors expressing shSCR or shSmad2. Real time qPCR was used to measure the mRNA expression of IL13Rα2. Asterisk ( * ) indicates a statistically significant difference between MIV-shSCR and MIV-shSmad2 ( n = 3; p < 0.05). (E) Western blotting showing the protein expression of Smad2 and IL13Rα2 in MIV-shSCR and MIV-shSmad2 cells. Antibody against β-tubulin was used as a loading control. Protein expression was quantified using ImageJ software.

Article Snippet: To study the effects of small molecule inhibitors on Activin A-induced gene expression, MII cells were serum starved in 0.2% HS-containing DMEM/F12 overnight and then treated with 1 μM EW-7197 (TargetMol), 1 μM SB-505124 (TargetMol) or 10 ng/ml Activin A alone or in combination (as indicated in respective figures).

Techniques: Expressing, Cell Culture, Western Blot, Software, Stable Transfection, Transduction

Journal: Signal Transduction and Targeted Therapy

Article Title: Targeting cytokine and chemokine signaling pathways for cancer therapy

doi: 10.1038/s41392-024-01868-3

Figure Lengend Snippet: Agents targeting TGF-β in preclinical or clinical studies

Article Snippet: TGFβRI , Receptor kinase inhibitor , Vactosertib , MedPacto.

Techniques:

Journal: Frontiers in Cardiovascular Medicine

Article Title: Microvascular significance of TGF-β axis activation in COVID-19

doi: 10.3389/fcvm.2022.1054690

Figure Lengend Snippet: Transforming growth factor-beta (TGF-β) pathway inhibitors (approved, currently in clinical trials, or preclinical) potentially relevant to COVID-19 prevention or treatment.

Article Snippet: Vactosertib (TEW7197) , Bristol Myers Squibb (Forbius) , Oral , Small molecule, TGFβRIi , Investigational cancer , Of 17 trials: NCT03074006 NCT04515979 , Phase 2 Ongoing or completed/Unpublished.

Techniques: Clinical Proteomics, Activation Assay, In Vivo

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Completed clinical trials that evaluated TGF-β pathway antagonists in oncology

Article Snippet: Based upon impressive preclinical and translational studies, Vactosertib has been combined with the immunomodulatory agent Pomalidomide (Pom, Pomalyst, Bristol-Myers Squibb) in a phase Ib/IIa study to treat participants with relapsed and/or refractory MM (NCT03143985) [ , ].

Techniques: Clinical Proteomics, Drug discovery, Control, Vaccines, Inhibition

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Ongoing clinical trials to evaluate TGF-β pathway antagonists in oncology

Article Snippet: Based upon impressive preclinical and translational studies, Vactosertib has been combined with the immunomodulatory agent Pomalidomide (Pom, Pomalyst, Bristol-Myers Squibb) in a phase Ib/IIa study to treat participants with relapsed and/or refractory MM (NCT03143985) [ , ].

Techniques: Clinical Proteomics, Biomarker Discovery, Vaccines, Histone Deacetylase Assay

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Tumor Intrinsic and Extrinsic Effects of Vactosertib. Vactosertib exerts potent antitumor effects (indicated in red) directly on cancer cells as well as on a number of other cell types

Article Snippet: Based upon impressive preclinical and translational studies, Vactosertib has been combined with the immunomodulatory agent Pomalidomide (Pom, Pomalyst, Bristol-Myers Squibb) in a phase Ib/IIa study to treat participants with relapsed and/or refractory MM (NCT03143985) [ , ].

Techniques:

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Completed clinical trials that evaluated TGF-β pathway antagonists in oncology

Article Snippet: Safety and efficacy of Vactosertib combined with Durvalumab (Imfinzi, Medimmune, AstraZeneca), a human mAb directed against programmed death-ligand 1 (PD-L1), was evaluated in patients with metastatic non-small cell lung cancer (NSCLC) and urothelial carcinoma (NCT03732274, [ ]).

Techniques: Clinical Proteomics, Drug discovery, Control, Vaccines, Inhibition

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Ongoing clinical trials to evaluate TGF-β pathway antagonists in oncology

Article Snippet: Safety and efficacy of Vactosertib combined with Durvalumab (Imfinzi, Medimmune, AstraZeneca), a human mAb directed against programmed death-ligand 1 (PD-L1), was evaluated in patients with metastatic non-small cell lung cancer (NSCLC) and urothelial carcinoma (NCT03732274, [ ]).

Techniques: Clinical Proteomics, Biomarker Discovery, Vaccines, Histone Deacetylase Assay

Journal: Journal of Hematology & Oncology

Article Title: Novel therapies emerging in oncology to target the TGF-β pathway

doi: 10.1186/s13045-021-01053-x

Figure Lengend Snippet: Tumor Intrinsic and Extrinsic Effects of Vactosertib. Vactosertib exerts potent antitumor effects (indicated in red) directly on cancer cells as well as on a number of other cell types

Article Snippet: Safety and efficacy of Vactosertib combined with Durvalumab (Imfinzi, Medimmune, AstraZeneca), a human mAb directed against programmed death-ligand 1 (PD-L1), was evaluated in patients with metastatic non-small cell lung cancer (NSCLC) and urothelial carcinoma (NCT03732274, [ ]).

Techniques:

Journal: Scientific Reports

Article Title: Differential kinase activity of ACVR1 G328V and R206H mutations with implications to possible TβRI cross-talk in diffuse intrinsic pontine glioma

doi: 10.1038/s41598-020-63061-0

Figure Lengend Snippet: Dose response of SF8628 DIPG cell viability. ( a ) Single agent study of TβRI inhibitors. * p < 0.05, ** p < 0.01, *** p < 0.001, n = 4, unpaired t -test of highest dose vs. control. ( b ) panobinostat and (c) GSK-J4 tested in combination with 10 µM TβRI inhibitors. The relative cell viability of drug(s) treated samples over the DMSO control is shown. When, as in ( c ) for EW7197, the IC50 value is inconclusive from curve fitting, an apparent upper limit is estimated.

Article Snippet: The TβRI inhibitors EW7197 (vactosertib), LY3200882 and LY2157299 (galunisertib), SB525334, histone deacetylase inhibitor panobinostat and histone demethylase inhibitor GSK-J4 (all from Fisher Scientific, USA and manufactured by Cayman Chemicals) were administered as drug treatments to assess their effects on SF8628 cell growth.

Techniques: Control

Journal: Frontiers in Immunology

Article Title: TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy

doi: 10.3389/fimmu.2022.1061394

Figure Lengend Snippet: The negative effects of TGF-β signaling on anti-tumor immunity. Pro-TGF-β contains a long signal sequence, a long N-terminal sequence named latency-associated peptide (LAP), and a short C-terminal, which is the mature cytokine. Then, dimerized pro-TGF-β is cleaved by Furin (a protease) in Golgi complex. As a result, the bioactive TGF-β moieties are linked with LAP homodimer through disulfide bonds. The LAP encircles bioactive TGF-β moiety and hampers the binding of TGF-β with its receptor. After secretion, The LAP homodimer could anchor to Glycoprotein A repetitions predominant (GARP) on Treg or crosslink with extracellular matrix by latent TGF-β binding proteins (LTBPs). Then, active TGF-β is released by integrin-transmitted forces when cell contraction. TGF-β signaling is triggered by the interaction of TGF-β ligands with TGF-β type II receptors (TGFβRII). Following the recruitment and phosphorylation of TGF-β type I receptors (TGFβRI) by TGFβRII, SMAD2 and SMAD3 are phosphorylated and further assembled into trimeric complexes with SMAD4. The SMAD complexes could translocate into cell nucleus and regulate the expression of TGF-β-targeted genes. TGF-β acts on various immune cells in the tumor microenvironment, inducing the generation of a suppressive immune microenvironment. On the one hand, TGF-β inhibits the cytotoxic activity of CD8 + T cells, CD4 + T cells, and NK cells. On the other hand, TGF-β increases the proportion of regulatory T cells (Treg) and M2-like macrophage. Moreover, recent studies have found that TGF-β modulates the activity of tumor-associated fibroblast (CAF) and increases the content of collagen fibers in the tumor stroma (contributed mainly by myCAF). The thickened collagen fibers surrounding the tumor tissue are detrimental to lymphocyte infiltration, resulting in an immune-excluded tumor type. Adapted from Bai et al, 2019 .

Article Snippet: Receptor kinase inhibitor , Vactosertib , TGFβRI , MedPacto.

Techniques: Sequencing, Binding Assay, Phospho-proteomics, Expressing, Activity Assay

Journal: Frontiers in Immunology

Article Title: TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy

doi: 10.3389/fimmu.2022.1061394

Figure Lengend Snippet: Agents targeting TGF-β signaling pathway.

Article Snippet: Receptor kinase inhibitor , Vactosertib , TGFβRI , MedPacto.

Techniques: