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Full-Text Articles in Medicine and Health Sciences
Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum
Microenvironment Generated During Egfr Targeted Killing Of Pancreatic Tumor Cells By Atc Inhibits Myeloid-Derived Suppressor Cells Through Cox2 And Pge2 Dependent Pathway, Archana Thakur, Dana Schalk, Elyse Tomaszewski, Sri Kondadasula, Hiroshi Yano, Fazlul H. Sarkar, Lawrence G. Lum
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Myeloid-derived suppressor cells (MDSCs) are one of the major components of the immune-suppressive network, play key roles in tumor progression and limit therapeutic responses. Recently, we reported that tumor spheres formed by breast cancer cell lines were visibly smaller in a Th1 enriched microenvironment with significantly reduced differentiation of MDSC populations in 3D culture. In this study, we investigated the mechanism(s) of bispecific antibody armed ATC mediated inhibition of MDSC in the presence or absence of Th1 microenvironment.
Methods
We used 3D co-culture model of peripheral blood mononuclear cells (PBMC) with pancreatic cancer cells MiaPaCa-2 [MiaE] …
Protein Tyrosine Phosphatase-1b Regulates The Tyrosine Phosphorylation Of The Adapter Grb2-Associated Binder 1 (Gab1) In The Retina, Ammaji Rajala, Ashok K. Dilly, Raju Vs Rajala
Protein Tyrosine Phosphatase-1b Regulates The Tyrosine Phosphorylation Of The Adapter Grb2-Associated Binder 1 (Gab1) In The Retina, Ammaji Rajala, Ashok K. Dilly, Raju Vs Rajala
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Gab1 (Grb2-associated binder 1) is a key coordinator that belongs to the insulin receptor substrate-1 like family of adaptor molecules and is tyrosine phosphorylated in response to various growth factors, cytokines, and numerous other molecules. Tyrosine phosphorylated Gab1 is able to recruit a number of signaling effectors including PI3K, SHP2 and PLC-γ. In this study, we characterized the localization and regulation of tyrosine phosphorylation of Gab1 in the retina.
Results
Our immuno localization studies suggest that Gab1 is expressed in rod photoreceptor inner segments. We found that hydrogen peroxide activates the tyrosine phosphorylation of Gab1 ex vivo and …
Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni
Pten Loss Mediated Akt Activation Promotes Prostate Tumor Growth And Metastasis Via Cxcl12/Cxcr4 Signaling, M Conley-Lacomb, Allen Saliganan, Pridvi Kandagatla, Yong Q. Chen, Michael L. Cher, Sreenivasa R. Chinni
Wayne State University Associated BioMed Central Scholarship
Abstract
Introduction
The chemokine CXCL12, also known as SDF-1, and its receptor, CXCR4, are overexpressed in prostate cancers and in animal models of prostate-specific PTEN deletion, but their regulation is poorly understood. Loss of the tumor suppressor PTEN (phosphatase and tensin homolog) is frequently observed in cancer, resulting in the deregulation of cell survival, growth, and proliferation. We hypothesize that loss of PTEN and subsequent activation of Akt, frequent occurrences in prostate cancer, regulate the CXCL12/CXCR4 signaling axis in tumor growth and bone metastasis.
Methods
Murine prostate epithelial cells from PTEN+/+, PTEN +/− , and PTEN−/− (prostate …
Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad
Systems Analysis Reveals A Transcriptional Reversal Of The Mesenchymal Phenotype Induced By Snail-Inhibitor Gn-25, Asfar S. Azmi, Aliccia Bollig-Fischer, Bin Bao, Bum-Joon Park, Sun-Hye Lee, Gyu Yong-Song, Gregory Dyson, Chandan K. Reddy, Fazlul H. Sarkar, Ramzi M. Mohammad
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
HMLEs (HMLE-SNAIL and Kras-HMLE, Kras-HMLE-SNAIL pairs) serve as excellent model system to interrogate the effect of SNAIL targeted agents that reverse epithelial-to-mesenchymal transition (EMT). We had earlier developed a SNAIL-p53 interaction inhibitor (GN-25) that was shown to suppress SNAIL function. In this report, using systems biology and pathway network analysis, we show that GN-25 could cause reversal of EMT leading to mesenchymal-to-epithelial transition (MET) in a well-recognized HMLE-SNAIL and Kras-HMLE-SNAIL models.
Results
GN-25 induced MET was found to be consistent with growth inhibition, suppression of spheroid forming capacity and induction of apoptosis. Pathway network analysis of mRNA expression …
Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar
Inhibition Of Hedgehog Signaling Sensitizes Nsclc Cells To Standard Therapies Through Modulation Of Emt-Regulating Mirnas, Aamir Ahmad, Ma'in Y. Maitah, Kevin R. Ginnebaugh, Yiwei Li, Bin Bao, Shirish M. Gadgeel, Fazlul H. Sarkar
Wayne State University Associated BioMed Central Scholarship
Abstract
Background
Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKIs) benefit Non-small cell lung cancer (NSCLC) patients, and an EGFR-TKIi erlotinib, is approved for patients with recurrent NSCLC. However, resistance to erlotinib is a major clinical problem. Earlier we have demonstrated the role of Hedgehog (Hh) signaling in Epithelial-to-Mesenchymal transition (EMT) of NSCLC cells, leading to increased proliferation and invasion. Here, we investigated the role of Hh signaling in erlotinib resistance of TGF-β1-induced NSCLC cells that are reminiscent of EMT cells.
Methods
Hh signaling was inhibited by specific siRNA and by GDC-0449, a small molecule antagonist of G protein coupled …