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The burden of breast cancer is imposing a huge global problem. Drug discovery research and novel approaches to treat breast cancer have been carried out extensively over the last decades. Although immune checkpoint inhibitors are showing promising preclinical and clinical results in treating breast cancer, they are facing multiple limitations. From an immunological perspective, a recent report highlighted breast cancer as an "inflamed tumor" with an immunosuppressive microenvironment. Consequently, researchers have been focusing on identifying novel immunological targets that can tune up the tumor immune microenvironment. In this context, several novel non-classical immune targets have been targeted to determine their ability to uncouple immunoregulatory pathways at play in the tumor microenvironment. This article will highlight strategies designed to increase the immunogenicity of the breast tumor microenvironment. It also addresses the latest studies on targets which can enhance immune responses to breast cancer and discusses examples of preclinical and clinical trial landscapes that utilize these targets. [ABSTRACT FROM AUTHOR]

Abstract: BACKGROUND: Green synthesis of silver nanoparticles (AgNPs) has become widely practiced worldwide. In this study, AgNPs were synthesized using a hot‐water extract of the edible mushroom Pleurotus sajor‐caju. The product, PSC‐AgNPs, was characterized by using UV–visible spectra, dynamic light scattering analysis, transmission electron microscopy (TEM), X‐ray diffraction (XRD) and Fourier transform infrared (FTIR) spectrometry. To assess its antifungal activity against Candida albicans, gene transcription and protein expression analyses were conducted for CaICL1 and its product, ICL, using real‐time quantitative polymerase chain reaction and western blot, respectively. RESULTS: PSC‐AgNPs with an average particle size of 11.68 nm inhibited the growth of the pathogenic yeast C. albicans. Values for minimum inhibitory concentration and minimum fungicidal concentration were 250 and 500 mg L−1, respectively. TEM images revealed that the average particle size of PSC‐AgNPs was 16.8 nm, with the values for zeta potential and the polydispersity index being −8.54 mV and 0.137, respectively. XRD and FTIR spectra showed PSC‐AgNPs to have a face‐centered cubic crystalline structure. The polysaccharides and amino acid residues present in P. sajor‐caju extract were found to be involved in reducing Ag+ to AgNP. Both CaICL1 transcription and ICL protein expression were found to be suppressed in the cells treated with PSC‐AgNPs as compared with the control. CONCLUSION: Our PSC‐AgNP preparation makes for a promising antifungal agent that can downregulate isocitrate lyase. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-angiogenic activity of a methanol leaf extract of Labisia pumila (ME), and its bioactive water fraction (WF), using in vitro models. Methods: The antioxidant activity and total phenolic contents of ME and WF were assessed using DPPH and Folin-Ciocalteu reagents. Antiproliferative effects of extracts towards human umbilical vein endothelial cells (HUVECs) were evaluated using MTT assay. Isolated rat aortic ring and matrigel tube formation assays were performed to assess the antiangiogenic potential of Me and its WF. Levels of VEGF protein in the cell lysates were measured using ELISA kit. Results: Among all the extracts prepared, ME and its WF showed higher total phenolic contents and exhibited moderate antioxidant effects. Significant (p < 0.001) suppression of microvessels outgrowth with half-maximal concentration (IC50) values of 20 and 26 μg/mL for ME and WF, was observed in rat aortic ring assay. ME and its WF halted proliferation and tube formation capacity of HUVECs in in vitro assays. Marked reduction in VEGF levels was observed in lysates of HUVECs treated with ME and its WF. Conclusion: Labisia pumila leaf extract and its water fraction halted angiogenesis by blocking VEGF secretion leading to inhibition of endothelial cells proliferation and differentiation which is suggested to be due to its phenolic antioxidant contents. [ABSTRACT FROM AUTHOR]

Background: A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication., Methods: The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones., Results: Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing., Conclusion: NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication., Competing Interests: Conflicts of Interest The authors declare no conflict of interest regarding the publication of this manuscript. Furthermore, the funding parties had no role in the design of the study; data collection, analysis and interpretation; the writing of the manuscript or the decision to publish the results.

Background: Cancer is characterized by uncontrolled cell division caused by dysregulation of cell proliferation. Therefore, agents that impair cancer cell proliferation could have potential therapeutic value. Higher plants are considered to be a good source of anticancer agents, and several clinically tested chemotherapeutic agents have been isolated from plants or derived from constituents of plant origin., Methods: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast)., Results: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells., Conclusion: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)