Orphan nuclear receptor TR3/Nur77 biologics inhibit tumor growth by targeting angiogenesis and tumor cells

Publication date: Available online 23 October 2019Source: Microvascular ResearchAuthor(s): Chen Chen, Yan Li, Shiqiang Hou, Pierre M. Bourbon, Liuliang Qin, Kevin Zhao, Taiyang Ye, Dezheng Zhao, Huiyan ZengAbstractPathological angiogenesis is a hallmark of many diseases. Previously, we reported that orphan nuclear receptor TR3/Nur77 was a critical mediator of angiogenesis to regulate tumor growth, sepsis and skin wound healing. However, none of the TR3/Nur77 targeting molecule has been in clinical trial so far. Here, we designed and generated novel TR3 shRNAs and two minigenes that had therapeutic potential for cancer treatment. In addition to extend our previous findings that tumor growth was inhibited in Nur77 knockout mice, we found that metastasis of colorectal tumor was completely inhibited in Nur77−/− mice. Tumor masses were increased ~70% and decreased ~40% in our transgenic EC-Nur77-S mice and EC-Nur77-DN mice, in which the full-length cDNA and the dominant negative mutant of TR3/Nur77 were inducibly and specifically expressed in mouse endothelium, respectively. TR3 was highly expressed in the vasculature and tumor cells of human melanoma and colorectal cancer tissues, but not in normal tissues. The novel TR3 shRNAs and two minigenes almost completely inhibited the proliferation and migration of HUVECs and human melanoma A375sm cells. Angiogenesis induced by adenoviruses expressing VEGF and melanoma growth in mice were greatly and significantly inhibited b...
Source: Microvascular Research - Category: Biochemistry Source Type: research

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Publication date: January 2020Source: Trends in Food Science &Technology, Volume 95Author(s): Ali Atamaleki, Mohsen Sadani, Amir Raoofi, Ali Miri, Saeed Gharibian Bajestani, Yadolah Fakhri, Zoha Heidarinejad, Amin Mousavi KhaneghahAbstractBackgroundThere is an increasing trend in the consumption of egg on a worldwide scale, however, it can be a source of potentially toxic elements (PTEs) which could threaten the health of consumers.Scope and approachThe related studies on the concentration of PTEs in eggs by databases including PubMed, Scopus, Web of Science and Embase in a global scale were retrieved and following met...
Source: Trends in Food Science and Technology - Category: Food Science Source Type: research
Publication date: Available online 8 November 2019Source: Food Research InternationalAuthor(s): Rodrigo Rezende Cardoso, Rafaela Oliveira Neto, Carolina Thomaz dos Santos D'Almeida, Talita Pimenta do Nascimento, Carolina Girotto Pressete, Luciana Azevedo, Hercia Stampini Duarte Martino, Luiz Claudio Cameron, Mariana Simões Larraz Ferreira, Frederico Augusto Ribeiro de BarrosAbstractUPLC-QTOF-MSE phenolic profile of kombuchas produced from the fermentation of green tea or black tea at 25°C for 10 days was investigated along with the determination of their antioxidant capacities, antibacterial and antiproliferativ...
Source: Food Research International - Category: Food Science Source Type: research
Publication date: Available online 13 November 2019Source: Current Opinion in VirologyAuthor(s): Marta M Gaglia, Karl Munger
Source: Current Opinion in Virology - Category: Virology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Future Perspectives It is now evident that NK/ILC family plays a pivotal role in the immune defenses. Recent studies in murine and human settings demonstrated that the expression of several inhibitory checkpoints, that may be detrimental in the tumor context, is not restricted to T lymphocytes, revealing an important, yet poorly appreciated, contribution of their expression on innate immune cells. Thus, in the recent years different immunotherapy approaches, based on the blockade of inhibitory NK cell receptors, have been developed in order to unleash NK cell cytotoxicity. This is particularly important in...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Laure Garnier*, Anastasia-Olga Gkountidi and Stephanie Hugues* Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland The lymphatic system comprises a network of lymphoid tissues and vessels that drains the extracellular compartment of most tissues. During tumor development, lymphatic endothelial cells (LECs) substantially expand in response to VEGFR-3 engagement by VEGF-C produced in the tumor microenvironment, a process known as tumor-associated lymphangiogenesis. Lymphatic drainage from the tumor to the draining lymph nodes consequently increases, powering inters...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Authors: Neukirch L, Nielsen TK, Laursen H, Daradoumis J, Thirion C, Holst PJ Abstract Endogenous retroviruses (ERVs) that make up 8% of the human genome have been associated with the development and progression of cancer. The murine model system of the melanoma associated retrovirus (MelARV), which is expressed in different murine cancer cell lines, can be used to study mechanisms and therapeutic approaches against ERVs in cancer. We designed a vaccine strategy (Ad5-MelARV) of adenoviruses encoding the MelARV proteins Gag and Env that assemble in vivo into virus-like particles displaying the cancer-associated MelA...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Cappuccini F, Pollock E, Stribbling S, Hill AVS, Redchenko I Abstract The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attrib...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
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