Systemic Delivery of Oncolytic Viruses: Hopes and Hurdles

Despite recent advances in both surgery and chemoradiotherapy, mortality rates for advanced cancer remain high. There is a pressing need for novel therapeutic strategies; one option is systemic oncolytic viral therapy. Intravenous administration affords the opportunity to treat both the primary tumour and any metastatic deposits simultaneously. Data from clinical trials have shown that oncolytic viruses can be systemically delivered safely with limited toxicity but the results are equivocal in terms of efficacy, particularly when delivered with adjuvant chemotherapy. A key reason for this is the rapid clearance of the viruses from the circulation before they reach their targets. This phenomenon is mainly mediated through neutralising antibodies, complement activation, antiviral cytokines, and tissue-resident macrophages, as well as nonspecific uptake by other tissues such as the lung, liver and spleen, and suboptimal viral escape from the vascular compartment. A range of methods have been reported in the literature, which are designed to overcome these hurdles in preclinical models. In this paper, the potential advantages of, and obstacles to, successful systemic delivery of oncolytic viruses are discussed. The next stage of development will be the commencement of clinical trials combining these novel approaches for overcoming the barriers with systemically delivered oncolytic viruses

The capability of heterogeneous γδ T cells in cancer treatment

γδ T cells, a specialized subset of T lymphocytes, have garnered significant attention within the realm of cancer immunotherapy. Operating at the nexus between adaptive and innate immunological paradigms, these cells showcase a profound tumor discernment repertoire, hinting at novel immunotherapeutic strategies. Significantly, these cells possess the capability to directly identify and eliminate tumor cells without reliance on HLA-antigen presentation. Furthermore, γδ T cells have the faculty to present tumor antigens to αβ T cells, amplifying their anti-tumoral efficacy.Within the diverse and heterogeneous subpopulations of γδ T cells, distinct immune functionalities emerge, manifesting either anti-tumor or pro-tumor roles within the tumor microenvironment. Grasping and strategically harnessing these heterogeneous γδ T cell cohorts is pivotal to their integration in tumor-specific immunotherapeutic modalities. The aim of this review is to describe the heterogeneity of the γδ T cell lineage and the functional plasticity it generates in the treatment of malignant tumors. This review endeavors to elucidate the intricate heterogeneity inherent to the γδ T cell lineage, the consequential functional dynamics in combating malignancies, the latest advancements from clinical trials, and the evolving landscape of γδ T cell-based oncological interventions, while addressing the challenges impeding the field

Syrian hamster as an ideal animal model for evaluation of cancer immunotherapy

Cancer immunotherapy (CIT) has emerged as an exciting new pillar of cancer treatment. Although benefits have been achieved in individual patients, the overall response rate is still not satisfactory. To address this, an ideal preclinical animal model for evaluating CIT is urgently needed. Syrian hamsters present similar features to humans with regard to their anatomy, physiology, and pathology. Notably, the histological features and pathological progression of tumors and the complexity of the tumor microenvironment are equivalent to the human scenario. This article reviews the current tumor models in Syrian hamster and the latest progress in their application to development of tumor treatments including immune checkpoint inhibitors, cytokines, adoptive cell therapy, cancer vaccines, and oncolytic viruses. This progress strongly advocates Syrian hamster as an ideal animal model for development and assessment of CIT for human cancer treatments. Additionally, the challenges of the Syrian hamster as an animal model for CIT are also discussed

Pancreatic Expression database: a generic model for the organization, integration and mining of complex cancer datasets

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the 5th leading cause of cancer death in both males and females. In recent years, a wealth of gene and protein expression studies have been published broadening our understanding of pancreatic cancer biology. Due to the explosive growth in publicly available data from multiple different sources it is becoming increasingly difficult for individual researchers to integrate these into their current research programmes. The Pancreatic Expression database, a generic web-based system, is aiming to close this gap by providing the research community with an open access tool, not only to mine currently available pancreatic cancer data sets but also to include their own data in the database.</p> <p>Description</p> <p>Currently, the database holds 32 datasets comprising 7636 gene expression measurements extracted from 20 different published gene or protein expression studies from various pancreatic cancer types, pancreatic precursor lesions (PanINs) and chronic pancreatitis. The pancreatic data are stored in a data management system based on the BioMart technology alongside the human genome gene and protein annotations, sequence, homologue, SNP and antibody data. Interrogation of the database can be achieved through both a web-based query interface and through web services using combined criteria from pancreatic (disease stages, regulation, differential expression, expression, platform technology, publication) and/or public data (antibodies, genomic region, gene-related accessions, ontology, expression patterns, multi-species comparisons, protein data, SNPs). Thus, our database enables connections between otherwise disparate data sources and allows relatively simple navigation between all data types and annotations.</p> <p>Conclusion</p> <p>The database structure and content provides a powerful and high-speed data-mining tool for cancer research. It can be used for target discovery i.e. of biomarkers from body fluids, identification and analysis of genes associated with the progression of cancer, cross-platform meta-analysis, SNP selection for pancreatic cancer association studies, cancer gene promoter analysis as well as mining cancer ontology information. The data model is generic and can be easily extended and applied to other types of cancer. The database is available online with no restrictions for the scientific community at <url>http://www.pancreasexpression.org/</url>.</p

The Impact of Temporal Geopotential Variations on GPS

Lemoine et al. (2006) and Lemoine et al. (2010) showed that applying more detailed models of time-variable gravity (TVG) improved the quality of the altimeter satellite orbits (e.g. TOPEX/Poseidon, Jason-1, Jason-2). This modeling include application of atmospheric gravity derived from 6-hrly pressure fields obtained from the ECMWF and annual gravity variations to degree & order 20x20 in spherical harmonics derived from GRACE data. This approach allowed the development of a consistent geophysical model for application to altimeter satellite orbit determination from 1993 to 2011. In addition, we have also evaluated the impact of TVG modeling on the POD of Jason-1 and Jason-2 by application of a weekly degree & order four gravity coefficient time series developed using data from ten SLR & DORIS-tracked satellites from 1993 to 2011 (Lemoine et al., 2011)

High-resolution Local Gravity Model of the South Pole of the Moon from GRAIL Extended Mission Data

We estimated a high-resolution local gravity field model over the south pole of the Moon using data from the Gravity Recovery and Interior Laboratory's extended mission. Our solution consists of adjustments with respect to a global model expressed in spherical harmonics. The adjustments are expressed as gridded gravity anomalies with a resolution of 1/6deg by 1/6deg (equivalent to that of a degree and order 1080 model in spherical harmonics), covering a cap over the south pole with a radius of 40deg. The gravity anomalies have been estimated from a short-arc analysis using only Ka-band range-rate (KBRR) data over the area of interest. We apply a neighbor-smoothing constraint to our solution. Our local model removes striping present in the global model; it reduces the misfit to the KBRR data and improves correlations with topography to higher degrees than current global models

Global and Local Gravity Field Models of the Moon Using GRAIL Primary and Extended Mission Data

The Gravity Recovery and Interior Laboratory (GRAIL) mission was designed to map the structure of the lunar interior from crust to core and to advance the understanding of the Moon's thermal evolution by producing a high-quality, high-resolution map of the gravitational field of the Moon. The mission consisted of two spacecraft, which were launched in September 2011 on a Discovery-class NASA mission. Ka-band tracking between the two satellites was the single science instrument, augmented by tracking from Earth using the Deep Space Network (DSN)

Physical modeling of unsteady turbulence in breaking tidal bores

A tidal bore is an unsteady flow motion generated by the rapid water level rise at the river mouth during the early flood tide under macrotidal and appropriate bathymetric conditions. This paper presents a study that physically investigates the turbulent properties of tidal bores. Results from some experimental measurements of free-surface fluctuations and turbulent velocities conducted on smooth and rough beds are reported. The free-surface measurements were conducted with Froude numbers of 1-1.7. Both undular and breaking bores were observed. Using an ensemble-averaging technique, the free-surface fluctuations of breaking tidal bores are characterized. Immediately before the roller, the free-surface curves gradually upwards. The passage of the bore roller is associated with some large water elevation fluctuations; the largest free-surface fluctuations are observed during the first half of the bore roller. The turbulent velocity measurements were performed at several vertical elevations during and shortly after the passage of breaking bores. Both the instantaneous and ensemble-averaged velocity data highlight a strong flow deceleration at all elevations during the bore passage. Close to the bed, the longitudinal velocity component becomes negative immediately after the roller passage, implying the existence of a transient recirculation. The height and duration of the transient are a function of the bed roughness, with a higher and longer recirculation region above the rough bed. The vertical velocity data presented some positive, upward motion beneath the front with increasing maximum vertical velocity with increasing distance from the bed. The transverse velocity data show some large fluctuations with nonzero ensemble average after the roller passage that highlight some intense secondary motion advected behind the bore front. DOI: 10.1061/(ASCE)HY.1943-7900.0000542. (C) 2012 American Society of Civil Engineers

Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles

Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses

A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.

© 2014 Haider et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Improved usage of the repertoires of pancreatic ductal adenocarcinoma (PDAC) profiles is crucially needed to guide the development of predictive and prognostic tools that could inform the selection of treatment options