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Biomedicines, Volume 5, Issue 1 (March 2017)

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Editorial

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Open AccessEditorial Acknowledgement to Reviewers of Biomedicines in 2016
Biomedicines 2017, 5(1), 6; doi:10.3390/biomedicines5010006
Received: 12 January 2017 / Revised: 12 January 2017 / Accepted: 12 January 2017 / Published: 12 January 2017
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Abstract The editors of Biomedicines would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article

Research

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Open AccessCommunication Nano-Magnetic Resonance Imaging (Nano-MRI) Gives Personalized Medicine a New Perspective
Biomedicines 2017, 5(1), 7; doi:10.3390/biomedicines5010007
Received: 5 November 2016 / Revised: 2 January 2017 / Accepted: 22 January 2017 / Published: 1 February 2017
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Abstract
This paper reviews some of the major and most recent advances in nanoscale-magnetic resonance imaging (nano-MRI) for personalized medicine (PM). Nano-MRI may drastically expand the capabilities of the traditional magnetic resonance images (MRI), down to the nanometer scale and possibly, in the near
[...] Read more.
This paper reviews some of the major and most recent advances in nanoscale-magnetic resonance imaging (nano-MRI) for personalized medicine (PM). Nano-MRI may drastically expand the capabilities of the traditional magnetic resonance images (MRI), down to the nanometer scale and possibly, in the near future, at the atomic scale. Nano-MRI is potentially able to observe structures which cannot be seen using today’s molecular imaging, with sensitivities of many billions of times better than MRI as currently used in hospitals, for example. The paper briefly reports on the foremost research themes in nano-MRI. Full article
(This article belongs to the Special Issue Molecular Imaging as a Tool for Personalized Medicine)
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Review

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Open AccessReview Targeting Autophagy for Oncolytic Immunotherapy
Biomedicines 2017, 5(1), 5; doi:10.3390/biomedicines5010005
Received: 18 November 2016 / Revised: 22 December 2016 / Accepted: 4 January 2017 / Published: 11 January 2017
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Abstract
Oncolytic viruses (OVs) are capable of exerting anti-cancer effects by a variety of mechanisms, including immune-mediated tumor cell death, highlighting their potential use in immunotherapy. Several adaptation mechanisms such as autophagy contribute to OV-mediated anti-tumor properties. Autophagy regulates immunogenic signaling during cancer therapy
[...] Read more.
Oncolytic viruses (OVs) are capable of exerting anti-cancer effects by a variety of mechanisms, including immune-mediated tumor cell death, highlighting their potential use in immunotherapy. Several adaptation mechanisms such as autophagy contribute to OV-mediated anti-tumor properties. Autophagy regulates immunogenic signaling during cancer therapy which can be utilized to design therapeutic combinations using approaches that either induce or block autophagy to potentiate the therapeutic efficacy of OVs. In this article, we review the complicated interplay between autophagy, cancer, immunity, and OV, summarize recent progress in the contribution of OV-perturbed autophagy to oncolytic immunity, and discuss the challenges in targeting autophagy to enhance oncolytic immunotherapy. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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Open AccessReview The Current Use of Stem Cells in Bladder Tissue Regeneration and Bioengineering
Biomedicines 2017, 5(1), 4; doi:10.3390/biomedicines5010004
Received: 31 October 2016 / Revised: 23 December 2016 / Accepted: 26 December 2016 / Published: 6 January 2017
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Abstract
Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe
[...] Read more.
Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe and reliable bladder tissue. Advancements in stem cell biology have catapulted stem cells to the center of many current tissue regeneration and bioengineering strategies. This review presents the recent advancements in the use of stem cells in bladder tissue bioengineering. Full article
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Open AccessReview Aptamer Technology: Adjunct Therapy for Malaria
Biomedicines 2017, 5(1), 1; doi:10.3390/biomedicines5010001
Received: 7 November 2016 / Revised: 8 December 2016 / Accepted: 16 December 2016 / Published: 4 January 2017
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Abstract
Malaria is a life-threatening parasitic infection occurring in the endemic areas, primarily in children under the age of five, pregnant women, and patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV)/(AIDS) as well as non-immune individuals. The cytoadherence of infected erythrocytes (IEs)
[...] Read more.
Malaria is a life-threatening parasitic infection occurring in the endemic areas, primarily in children under the age of five, pregnant women, and patients with human immunodeficiency virus and acquired immunodeficiency syndrome (HIV)/(AIDS) as well as non-immune individuals. The cytoadherence of infected erythrocytes (IEs) to the host endothelial surface receptor is a known factor that contributes to the increased prevalence of severe malaria cases due to the accumulation of IEs, mainly in the brain and other vital organs. Therefore, further study is needed to discover a new potential anti-adhesive drug to treat severe malaria thus reducing its mortality rate. In this review, we discuss how the aptamer technology could be applied in the development of a new adjunct therapy for current malaria treatment. Full article
(This article belongs to the Special Issue Engineering Aptamers for Biomedical Applications)
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Open AccessReview Designing the Sniper: Improving Targeted Human Cytolytic Fusion Proteins for Anti-Cancer Therapy via Molecular Simulation
Biomedicines 2017, 5(1), 9; doi:10.3390/biomedicines5010009
Received: 30 December 2016 / Revised: 27 January 2017 / Accepted: 10 February 2017 / Published: 17 February 2017
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Abstract
Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or
[...] Read more.
Targeted human cytolytic fusion proteins (hCFPs) are humanized immunotoxins for selective treatment of different diseases including cancer. They are composed of a ligand specifically binding to target cells genetically linked to a human apoptosis-inducing enzyme. hCFPs target cancer cells via an antibody or derivative (scFv) specifically binding to e.g., tumor associated antigens (TAAs). After internalization and translocation of the enzyme from endocytosed endosomes, the human enzymes introduced into the cytosol are efficiently inducing apoptosis. Under in vivo conditions such enzymes are subject to tight regulation by native inhibitors in order to prevent inappropriate induction of cell death in healthy cells. Tumor cells are known to upregulate these inhibitors as a survival mechanism resulting in escape of malignant cells from elimination by immune effector cells. Cytosolic inhibitors of Granzyme B and Angiogenin (Serpin P9 and RNH1, respectively), reduce the efficacy of hCFPs with these enzymes as effector domains, requiring detrimentally high doses in order to saturate inhibitor binding and rescue cytolytic activity. Variants of Granzyme B and Angiogenin might feature reduced affinity for their respective inhibitors, while retaining or even enhancing their catalytic activity. A powerful tool to design hCFPs mutants with improved potency is given by in silico methods. These include molecular dynamics (MD) simulations and enhanced sampling methods (ESM). MD and ESM allow predicting the enzyme-protein inhibitor binding stability and the associated conformational changes, provided that structural information is available. Such “high-resolution” detailed description enables the elucidation of interaction domains and the identification of sites where particular point mutations may modify those interactions. This review discusses recent advances in the use of MD and ESM for hCFP development from the viewpoints of scientists involved in both fields. Full article
(This article belongs to the Special Issue Targeted Human Cytolytic Fusion Proteins)
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Open AccessFeature PaperReview Viroimmunotherapy of Thoracic Cancers
Biomedicines 2017, 5(1), 2; doi:10.3390/biomedicines5010002
Received: 13 September 2016 / Revised: 24 November 2016 / Accepted: 24 November 2016 / Published: 4 January 2017
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Abstract
Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases
[...] Read more.
Thoracic cancers, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and malignant pleural mesothelioma (MM), cause the highest rate of cancer mortality worldwide. Most of these deaths are as a result of NSCLC; however, prognoses for the other two diseases remain as some of the poorest of any cancers. Recent advances in immunotherapy, specifically immune checkpoint inhibitors, have begun to help a small population of patients with advanced lung cancer. People who respond to these immune therapies generally have a durable response and many see dramatic decreases in their disease. However, response to immune therapies remains relatively low. Therefore, intense research is now underway to rationally develop combination therapies to expand the range of patients who will respond to and benefit from immune therapy. One promising approach is with oncolytic viruses. These oncolytic viruses (OVs) have been found to be selective for or have been engineered to preferentially infect and kill cancer cells. In pre-clinical models of different thoracic cancers, it has been found that these viruses can induce immunogenic cell death, increase the number of immune mediators brought into the tumor microenvironment and broaden the neoantigen-specific T cell response. We will review here the literature regarding the application of virotherapy toward augmenting immune responses in thoracic cancers. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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Open AccessFeature PaperReview Taking a Stab at Cancer; Oncolytic Virus-Mediated Anti-Cancer Vaccination Strategies
Biomedicines 2017, 5(1), 3; doi:10.3390/biomedicines5010003
Received: 27 November 2016 / Revised: 20 December 2016 / Accepted: 22 December 2016 / Published: 4 January 2017
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Abstract
Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer
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Vaccines have classically been used for disease prevention. Modern clinical vaccines are continuously being developed for both traditional use as well as for new applications. Typically thought of in terms of infectious disease control, vaccination approaches can alternatively be adapted as a cancer therapy. Vaccines targeting cancer antigens can be used to induce anti-tumour immunity and have demonstrated therapeutic efficacy both pre-clinically and clinically. Various approaches now exist and further establish the tremendous potential and adaptability of anti-cancer vaccination. Classical strategies include ex vivo-loaded immune cells, RNA- or DNA-based vaccines and tumour cell lysates. Recent oncolytic virus development has resulted in a surge of novel viruses engineered to induce powerful tumour-specific immune responses. In addition to their use as cancer vaccines, oncolytic viruses have the added benefit of being directly cytolytic to cancer cells and thus promote antigen recognition within a highly immune-stimulating tumour microenvironment. While oncolytic viruses are perfectly equipped for efficient immunization, this complicates their use upon previous exposure. Indeed, the host’s anti-viral counter-attacks often impair multiple-dosing regimens. In this review we will focus on the use of oncolytic viruses for anti-tumour vaccination. We will explore different strategies as well as ways to circumvent some of their limitations. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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Open AccessReview Oncolytic Vesicular Stomatitis Virus as a Viro-Immunotherapy: Defeating Cancer with a “Hammer” and “Anvil”
Biomedicines 2017, 5(1), 8; doi:10.3390/biomedicines5010008
Received: 20 December 2016 / Revised: 26 January 2017 / Accepted: 3 February 2017 / Published: 10 February 2017
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Abstract
Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse tumor cells, but to their potential to stimulate antitumor immune responses directed against the tumor. Vesicular stomatitis virus (VSV), a negative-strand RNA
[...] Read more.
Oncolytic viruses have gained much attention in recent years, due, not only to their ability to selectively replicate in and lyse tumor cells, but to their potential to stimulate antitumor immune responses directed against the tumor. Vesicular stomatitis virus (VSV), a negative-strand RNA virus, is under intense development as an oncolytic virus due to a variety of favorable properties, including its rapid replication kinetics, inherent tumor specificity, and its potential to elicit a broad range of immunomodulatory responses to break immune tolerance in the tumor microenvironment. Based on this powerful platform, a multitude of strategies have been applied to further improve the immune-stimulating potential of VSV and synergize these responses with the direct oncolytic effect. These strategies include: 1. modification of endogenous virus genes to stimulate interferon induction; 2. virus-mediated expression of cytokines or immune-stimulatory molecules to enhance anti-tumor immune responses; 3. vaccination approaches to stimulate adaptive immune responses against a tumor antigen; 4. combination with adoptive immune cell therapy for potentially synergistic therapeutic responses. A summary of these approaches will be presented in this review. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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Open AccessFeature PaperReview The Continued Promise and Many Disappointments of Oncolytic Virotherapy in Gastrointestinal Malignancies
Biomedicines 2017, 5(1), 10; doi:10.3390/biomedicines5010010
Received: 11 January 2017 / Revised: 23 February 2017 / Accepted: 28 February 2017 / Published: 4 March 2017
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Abstract
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium
[...] Read more.
Oncolytic virotherapy represents a novel therapeutic strategy in the treatment of gastrointestinal malignancies. Oncolytic viruses, including genetically engineered and naturally occurring viruses, can selectively replicate in and induce tumor cell apoptosis without harming normal tissues, thus offering a promising tool in the armamentarium for cancer therapy. While this approach has garnered much interest over the past several decades, there has not been significant headway across various tumor types. The recent approval of talimogene laherparepvec, a second-generation oncolytic herpes simplex virus type-1, for the treatment of metastatic melanoma, confirms the therapeutic potential of oncolytic viral therapy. Herein, we will highlight and review the role of oncolytic viral therapy in gastrointestinal malignancies while discussing its limitations and potential alternative mechanisms to improve its treatment efficacy. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
Open AccessReview Viroimmunotherapy for Colorectal Cancer: Clinical Studies
Biomedicines 2017, 5(1), 11; doi:10.3390/biomedicines5010011
Received: 1 February 2017 / Accepted: 2 March 2017 / Published: 10 March 2017
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Abstract
Colorectal cancer is a leading cause of cancer incidence and death. Therapies for those with unresectable or recurrent disease are not considered curative at present. More effective and less toxic therapies are desperately needed. Historically, the immune system was thought to be an
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Colorectal cancer is a leading cause of cancer incidence and death. Therapies for those with unresectable or recurrent disease are not considered curative at present. More effective and less toxic therapies are desperately needed. Historically, the immune system was thought to be an enemy to oncolytic viral therapy. Thinking that oncolysis would be the only mechanism for cell death, oncolytic virologists theorized that immune clearance was a detriment to oncolysis. Recent advances in our understanding of the tumor microenvironment, and the interplay of tumor survival and a patient’s immune system have called into question our understanding of both arenas. It remains unclear what combination of restrictions or enhancements of innate and/or cell-mediated immunity can yield the highest likelihood of viral efficacy. This article reviews the variety of mechanisms explored for viruses such as immunotherapy for colorectal cancer. Full article
(This article belongs to the Special Issue Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer)
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