Dual roles of myeloid-derived suppressor cells in various diseases: a review.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that originate from bone marrow stem cells. In pathological conditions, such as autoimmune disorders, allergies, infections, and cancer, normal myelopoiesis is altered to facilitate the formation of MDSCs. MDSCs were first shown to promote cancer initiation and progression by immunosuppression with the assistance of various chemokines and cytokines.

Antitumor effect of 3-(quinolin-2-ylmethylene)-4,6-dimethyl-5-hydroxy-7-azaoxindole down-regulating the Gas6-Axl axis.

In this study, a new series of 3-arylidene-4,6-dimethyl-5-hydroxy-7-azaoxindole compounds with a wide range of functional groups were designed, synthesized, and evaluated for their antitumor activity. Among the 35 compounds, compound 6-15, with a quinoline moiety, showed cytotoxic IC values superior to those of sunitinib against the seven cancer cell lines (MCF-7, MDA-MB-231, HT-29, DU145, U937, A549, and PANC-1). However, its inhibitory activity against receptor tyrosine kinases (VEGFR2, PDGFRβ, c-KIT, FGFR1, FLT3, CSF1R, EGFR, Axl, and Axl mutant) was 100 -3000-fold weaker than that of sunitinib.

Diverse roles of tumor-stromal PDGFB-to-PDGFRβ signaling in breast cancer growth and metastasis.

Over the last couple of decades, it has become increasingly apparent that the tumor microenvironment (TME) mediates every step of cancer progression and solid tumors are only able to metastasize with a permissive TME. This intricate interaction of cancer cells with their surrounding TME, or stroma, is becoming more understood with an ever greater knowledge of tumor-stromal signaling pairs such as platelet-derived growth factors (PDGF) and their cognate receptors. We and others have focused our research efforts on understanding how tumor-derived PDGFB activates platelet-derived growth factor receptor beta (PDGFRβ) signaling specifically in the breast cancer TME.

Three-dimensional Angiogenesis Assay System using Co-culture Spheroids Formed by Endothelial Colony Forming Cells and Mesenchymal Stem Cells.

Studies in the field of angiogenesis have been aggressively growing in the last few decades with the recognition that angiogenesis is a hallmark of more than 50 different pathological conditions, such as rheumatoid arthritis, oculopathy, cardiovascular diseases, and tumor metastasis. During angiogenesis drug development, it is crucial to use in vitro assay systems with appropriate cell types and proper conditions to reflect the physiologic angiogenesis process. To overcome limitations of current in vitro angiogenesis assay systems using mainly endothelial cells, we developed a 3-dimensional (3D) co-culture spheroid sprouting assay system.

Identification of DNA and glutathione adducts in male Sprague-Dawley rats exposed to 1-bromopropane.

Occupational exposure of workers to 1-bromopropane (1-BP) has raised concerns in industry for many years. Despite the known toxicity of this chemical, molecular events attributed to exposure to 1-BP have not been extensively studied. The aim of the present study was to examine the effects of 1-BP exposure on adduct formation with DNA and glutathione (GSH) in male Sprague-Dawley rats in an attempt to determine the early stages of toxicity.

Two-Cell Spheroid Angiogenesis Assay System Using Both Endothelial Colony Forming Cells and Mesenchymal Stem Cells.

Most angiogenesis assays are performed using endothelial cells. However, blood vessels are composed of two cell types: endothelial cells and pericytes. Thus, co-culture of two vascular cells should be employed to evaluate angiogenic properties.

4-Hydroxynonenal-induced GPR109A (HCA receptor) activation elicits bipolar responses, G -mediated anti-inflammatory effects and G -mediated cell death.

Background And Purpose: In this study, we examined the possibility that 4-hydroxynonenal (4-HNE) acting as a ligand for the HCA receptor (GPR109A) elicits both anti-inflammatory and cell death responses.

Experimental Approach: Agonistic activity of 4-HNE was determined by observing the inhibition of cAMP generation in CHO-K1-GPR109A-G cell line, using surface plasmon resonance (SPR) binding and competition binding assays with [ H]-niacin. 4-HNE-mediated signalling pathways and cellular responses were investigated in cells expressing GPR109A and those not expressing these receptors.

5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: design, synthesis and cytotoxicity against cancer cells.

Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent®) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains.

The Anti-Tumor Activity of Succinyl Macrolactin A Is Mediated through the β-Catenin Destruction Complex via the Suppression of Tankyrase and PI3K/Akt.

Accumulated gene mutations in cancer suggest that multi-targeted suppression of affected signaling networks is a promising strategy for cancer treatment. In the present study, we report that 7-O-succinyl macrolactin A (SMA) suppresses tumor growth by stabilizing the β-catenin destruction complex, which was achieved through inhibition of regulatory components associated with the complex. SMA significantly reduced the activities of PI3K/Akt, which corresponded with a decrease in GSK3β phosphorylation, an increase in β-catenin phosphorylation, and a reduction in nuclear β-catenin content in HT29 human colon cancer cells.