Phenolic-rich apple extracts have photoprotective and anti-cancer effect in dermal cells.

Skin cancer is the most common type of malignancy in light-skinned populations and phenolics are promising anticarcinogenic agents.To characterise and evaluate the protective potential of apple extracts against the DNA damage caused by UV-radiation in culture of human fibroblasts as well as to verify the anticarcinogenic effect of these extracts in murine and human melanoma cells

Subcellular localization of PD‐L1 and cell‐cycle‐dependent expression of nuclear PD‐L1 variants: implications for head and neck cancer cell functions and therapeutic efficacy

The programmed cell death 1 ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) axis is primarily associated with immunosuppression in cytotoxic T lymphocytes (CTLs). However, mounting evidence is supporting the thesis that PD-L1 not only functions as a ligand but mediates additional cellular functions in tumor cells. Moreover, it has been demonstrated that PD-L1 is not exclusively localized at the cellular membrane. Subcellular fractionation revealed the presence of PD-L1 in various cellular compartments of six well-characterized head and neck cancer (HNC) cell lines, including the nucleus. Via Western blotting, we detected PD-L1 in its well-known glycosylated/deglycosylated state at 40–55 kDa. In addition, we detected previously unknown PD-L1 variants with a molecular weight at approximately 70 and > 150 kDa exclusively in nuclear protein fractions. These in vitro findings were confirmed with primary tumor samples from head and neck squamous cell carcinoma (HNSCC) patients. Furthermore, we demonstrated that nuclear PD-L1 variant expression is cell-cycle-dependent. Immunofluorescence staining of PD-L1 in different cell cycle phases of synchronized HNC cells supported these observations. Mechanisms of nuclear PD-L1 trafficking remain less understood; however, proximity ligation assays showed a cell-cycle-dependent interaction of the cytoskeletal protein vimentin with PD-L1, whereas vimentin could serve as a potential shuttle for nuclear PD-L1 transportation. Mass spectrometry after PD-L1 co-immunoprecipitation, followed by gene ontology analysis, indicated interaction of nuclear PD-L1 with proteins involved in DNA remodeling and messenger RNA (mRNA) splicing. Our results in HNC cells suggest a highly complex regulation of PD-L1 and multiple tumor cell-intrinsic functions, independent of immune regulation. These observations bear significant implications for the therapeutic efficacy of immune checkpoint inhibition

Potential Roles of Tumor Cell- and Stroma Cell-Derived Small Extracellular Vesicles in Promoting a Pro-Angiogenic Tumor Microenvironment

Simple Summary In this review, we focus on the distinct functions of tumor-cell-derived small extracellular vesicles in promotion of angiogenesis and describe their potential as a therapeutic target for anti-angiogenic therapies. Also, we focus on extracellular vesicles derived from non-cancer cells and their potential role in stimulating a pro-angiogenic tumor microenvironment. The article describes the biogenesis of small extracellular vesicles and refers to their proteomic cargo components that play a role in promoting angiogenesis. Moreover, we explain how small extracellular vesicles derived from tumors and non-cancer cells can interact with recipient cells and alter their functions. We particularly focus on phenotypical and functional changes in endothelial cells, macrophages, and neutrophils that result in proangiogenic signaling. Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. They are characterized by a distinct biogenesis and complex cargo composition, which reflects the cytosolic contents and cell-surface molecules of the parent cells. This cargo consists of proteins, nucleic acids, and lipids and is competent in inducing signaling cascades in recipient cells after surface interactions or in initiating the generation of a functional protein by delivering nucleic acids. Based on these characteristics, sEVs are now considered as important mediators of intercellular communication. One hallmark of sEVs is the promotion of angiogenesis. It was shown that sEVs interact with endothelial cells (ECs) and promote an angiogenic phenotype, ultimately leading to increased vascularization of solid tumors and disease progression. It was also shown that sEVs reprogram cells in the tumor microenvironment (TME) and act in a functionally cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from other cell types. In this review, we will focus on the distinct functions of tumor-cell-derived sEVs (TEX) in promotion of angiogenesis and describe their potential as a therapeutic target for anti-angiogenic therapies. Also, we will focus on non-cancer stroma-cell-derived small extracellular vesicles and their potential role in stimulating a pro-angiogenic TME

CD73-sirna loaded cationic nanoemulsion exhibits in vitro antiglioma activity

sem informaçãoGlioblastoma (GBM) is the most common malignant brain tumor characterized by high invasiveness, poor prognosis and limited therapeutic options. Gene expression knockdown using RNA interference tool (siRNA) has been proposed as new alternative for cancer t141S80S80sem informaçãosem informaçãosem informaçã

Endophytic Fungus Isolated From Achyrocline satureioides Exhibits Selective Antiglioma Activity - The Role of Sch-642305.

Made available in DSpace on 2019-01-11T00:04:15Z (GMT). No. of bitstreams: 1 ART18098.pdf: 5638786 bytes, checksum: 8c759ee5230bfa26121fea1f017f67c1 (MD5) Previous issue date: 2019-01-07bitstream/item/190237/1/ART18098.pd

Endophytic Fungus Isolated From Achyrocline satureioides Exhibits Selective Antiglioma Activity - The Role of Sch-642305.

Made available in DSpace on 2019-01-11T00:04:15Z (GMT). No. of bitstreams: 1 ART18098.pdf: 5638786 bytes, checksum: 8c759ee5230bfa26121fea1f017f67c1 (MD5) Previous issue date: 2019-01-07bitstream/item/190237/1/ART18098.pd