Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF.

Oncolytic vaccinia virus has been shown to induce a profound, rapid and tumor-specific vascular collapse in both preclinical models and clinical studies; however, a complete examination of the kinetics and levels of collapse and revascularization has not been described previously. Contrast-enhanced ultrasound was used to follow tumor perfusion levels in mouse tumor models at times after vaccinia therapy. It was observed that revascularization after viral therapy was dramatically delayed and did not occur until after viral clearance.

Arming viruses in multi-mechanistic oncolytic viral therapy: current research and future developments, with emphasis on poxviruses.

The field of oncolytic virology has made great strides in recent years. However, one key finding has been that the use of viral agents that replicate selectively in tumors is usually insufficient to achieve anything beyond small and transient responses. Instead, like most cancer therapies, oncolytic viruses are most effective in combination with other therapies, which is where they have proven therapeutic effects in clinical and preclinical studies.

Particularizing the general: Sustaining theoretical integrity in the context of an evidence-based practice agenda.

Proliferation of demands for accountability and health care quality places nurses under constant pressure to ensure professional practice is evidence-based. The corresponding emphasis on knowledge that pertains to general populations challenges nursing's traditional focus on the uniqueness of each individual patient. Considering how nurses engage with professional systematic thinking processes, we reflect on ways competing agendas in the evidence-based practice environment compromise the professional vision aspired to by an earlier era of nursing model and framework builders.

Changing communication needs and preferences across the cancer care trajectory: insights from the patient perspective.

Purpose: In this program of research, we sought to expand our understanding of how cancer patients' communication needs and preferences change across the course of their illness trajectory. To address known limitations in the empirical knowledge base, we designed a study capitalizing on representative patient reports as they occurred within time and across experience obtaining care for this disease.

Methods: We used a longitudinal cohort design informed by interpretive description methodology to follow 125 patients over a multi-year period as they reflected on their ongoing experiences with cancer care communication.

The role of GM-CSF in enhancing immunotherapy of cancer.

Evaluation of: Kanerva A, Nokisalmi P, Diaconu I et al. Antiviral and anti-tumor T-cell immunity in patients treated with GM-CSF coding oncolytic adenovirus. Clin.

Of Guinea pigs and gratitude: the difficult discourse of clinical trials from the cancer patient perspective.

In an ongoing longitudinal qualitative cohort study of cancer patients' needs and preferences across the cancer journey, we harvested a subset of accounts pertaining to conversations between patients and their clinicians around clinical trials. Recognising these conversations as a departure from the more routine discourses of clinical care, in that they enter into new dimensions of investment and motivation on the part of clinicians, we engaged in both secondary analysis of banked data and focussed interviewing of cancer patients to better understand how cancer patients describe communications in relation to decisions pertaining to clinical trials participation. Using constant comparative techniques informed by the interpretive description approach to applied qualitative methodology to guide a systematic analysis of this set of data, we documented patterns and themes across patient accounts.

Enhancement of head and neck squamous cell carcinoma proliferation, invasion, and metastasis by tumor-associated fibroblasts in preclinical models.

Background: Head and neck squamous cell carcinoma (HNSCC) has had little improvement in mortality rates in decades. A clearer understanding of the HNSCC tumor microenvironment will aid in finding more effective targeted therapies for this disease. Tumor-associated fibroblasts (TAFs) are the largest stromal cellular components of the tumor microenvironment in HNSCC.

Communication challenges for chronic metastatic cancer in an era of novel therapeutics.

Advances in the production of novel therapies for cancer management are creating new challenges for the support of increasing numbers of persons surviving for extended periods with advanced disease. Despite incurable and life-limiting metastatic conditions, these patients are living longer with serious disease, pushing the boundaries of what science explains and clinicians can confidently interpret using available evidence. Here we report findings from an early subset of such individuals within a longitudinal qualitative cancer cohort study on clinician-patient communication across the cancer trajectory.

A rationally designed A34R mutant oncolytic poxvirus: improved efficacy in peritoneal carcinomatosis.

Oncolytic poxviruses have demonstrated initial promising results in patients with cancer in clinical trials, yet further improvements are needed. It has been shown that a single point mutation in the A34R gene resulted in the production of more total progeny virus and more extracellular enveloped virus (EEV), a form that can be immune-evasive and with enhanced spread. We have genetically engineered a new oncolytic poxvirus (designated vA34R) by incorporating this mutated A34R gene into a viral backbone (vvDD) which was designed for tumor-selective replication.

Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans.

Efforts to selectively target and disrupt established tumor vasculature have largely failed to date. We hypothesized that a vaccinia virus engineered to target cells with activation of the ras/MAPK signaling pathway (JX-594) could specifically infect and express transgenes (hGM-CSF, β-galactosidase) in tumor-associated vascular endothelial cells in humans. Efficient replication and transgene expression in normal human endothelial cells in vitro required either VEGF or FGF-2 stimulation.

Poor communication in cancer care: patient perspectives on what it is and what to do about it.

Background: Communication in cancer care is a recognized problem for patients. Research to date has provided limited relevant knowledge toward solving this problem.

Objective: Our research program aims to understand helpful and unhelpful communication from the patient perspective and to document changes in patient needs and priorities over time.

Expression of CCL19 from oncolytic vaccinia enhances immunotherapeutic potential while maintaining oncolytic activity.

Promising phase II clinical results have been reported recently for several oncolytic viral therapeutics, including strains based on vaccinia virus. One reason for this has been an increased appreciation of the critical therapeutic importance of the immune response raised by these viruses. However, the most commonly used approaches to enhance these immunotherapeutic effects in oncolytic viruses, typically though expression of cytokine transgenes, often also result in a reduction in oncolytic activity and premature clearance of the virotherapy from the tumor.

Potential for enhanced therapeutic activity of biological cancer therapies with doxycycline combination.

Despite significant strides made in the clinical translation of adoptive immune cell therapies, it is apparent that many tumors incorporate strategies to avoid recognition by receptors expressed on the immune cells, such as NKG2D. Strategies that stabilize the expression of ligands for these receptors may enhance the therapeutic potential of these and related therapies. Doxycycline inhibits matrix metalloproteinases (MMPs) that act to cleave the extracellular domain of MICA/B, ligands for the NKG2D receptor.

Regulating cytokine function enhances safety and activity of genetic cancer therapies.

Genetic therapies, including transfected immune cells and viral vectors, continue to show clinical responses as systemically deliverable and targeted therapeutics, with the first such approaches having been approved for cancer treatment. The majority of these employ cytokine transgenes. However, expression of cytokines early after systemic delivery can result in increased toxicity and nonspecific induction of the immune response.

Crosstalk between immune cell and oncolytic vaccinia therapy enhances tumor trafficking and antitumor effects.

The combination of an oncolytic virus, that directly destroys tumor cells and mediates an acute immune response, with an immune cell therapy, capable of further enlisting and enhancing the host immune response, has the potential to create a potent therapeutic effect. We have previously developed several strategies for optimizing the delivery of oncolytic vaccinia virus vectors to their tumor targets, including the use of immune cell-based carrier vehicles and the incorporation of mutations that increase production of the enveloped form of vaccinia (extracellular enveloped viral (EEV)) that is better adapted to spread within a host. Here, we initially combine these approaches to create a novel therapeutic, consisting of an immune cell (cytokine-induced killer, CIK) preloaded with an oncolytic virus that is EEV enhanced.