TLR Agonist Nano Immune Therapy Clears Peritoneal and Systemic Ovarian Cancer.

Intraperitoneal (IP) administration of immunogenic mesoporous silica nanoparticles (iMSN) in a mouse model of metastatic ovarian cancer promotes the development of tumor-specific CD8 T cells and protective immunity. IP delivery of iMSN functionalized with the Toll-like receptor (TLR) agonists polyethyleneimine (PEI), CpG oligonucleotide, and monophosphoryl lipid A (MPLA) stimulated rapid uptake by all peritoneal myeloid subsets. Myeloid cells quickly transported iMSN to milky spots and fat-associated lymphoid clusters (FALCs) present in tumor-burdened adipose tissues, leading to a reduction in suppressive T cells and an increase in activated memory T cells.

The Combination of TIM3-Based Checkpoint Blockade and Oncolytic Virotherapy Regresses Established Solid Tumors.

T-cell immunoglobulin and mucin domain 3 (TIM3) is emerging as a potential target for antibody-based checkpoint blockade. However, the efficacy of TIM3 blockade in combination with other treatment modalities, has not been extensively studied. In the current work we combined TIM3 blockade with myxoma virus-based oncolytic virotherapy (OV).

Monitoring Therapeutic Responses to Silicified Cancer Cell Immunotherapy Using PET/MRI in a Mouse Model of Disseminated Ovarian Cancer.

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer.

Decreasing the Susceptibility of Malignant Cells to Infection Does Not Impact the Overall Efficacy of Myxoma Virus-Based Oncolytic Virotherapy.

Oncolytic virotherapy relies on the induction of anti-tumor immune responses to achieve therapeutic efficacy. The factors that influence the induction of these responses, however, are not well understood. To begin to address this lack of knowledge, we asked how decreasing the susceptibility of malignant cells to direct viral infection would impact the induction of immune responses and therapeutic efficacy caused by oncolytic myxoma virus treatment.

Initial dose of oncolytic myxoma virus programs durable antitumor immunity independent of in vivo viral replication.

Background: Oncolytic therapy uses live-replicating viruses to improve the immunological status of treated tumors. Critically, while these viruses are known to self-amplify in vivo, clinical oncolytic therapies still appear to display a strong dose dependence and the mechanisms mediating this dose dependence are not well understood.

Methods: To explore this apparent contradiction, we investigated how the initial dose of oncolytic myxoma virus affected the subsequent ability of treatment to alter the immunological status of tumors as well as synergize with programmed cell death protein 1 (PD1) blockade.

Reduced cellular binding affinity has profoundly different impacts on the spread of distinct poxviruses.

Poxviruses are large enveloped viruses that replicate exclusively in the cytoplasm. Like all viruses, their replication cycle begins with virion adsorption to the cell surface. Unlike most other viral families, however, no unique poxviral receptor has ever been identified.

Successful implantation of a Micra leadless pacemaker via collateral femoral vein and inferior vena cava filter.

This case details the successful implementation of a leadless pacemaker device in a patient with multiple venous occlusions and an IVC filter. As the incidence of IVC filters increases in patients with dysrhythmias, further investigations are required to determine the risk and safety of leadless pacemaker placement in this population.

Increased risk of mortality after lower extremity bypass in individuals with acute kidney injury in the Vascular Quality Initiative.

Objective: The development of acute kidney injury (AKI) and its effect on prognosis after lower extremity bypass (LEB) surgery have not been well described. We determined risk factors associated with AKI in patients undergoing infrainguinal LEB surgery and whether individuals with AKI are at increased risk for cardiovascular events and mortality.

Methods: Data for 12,907 operations entered in the Vascular Quality Initiative (VQI) registry from January 2012 through April 2015 were retrospectively reviewed.

Sinus of Valsalva Fistula to the Right Ventricle along with Coronary Artery Fistula to the Pulmonary Artery in a Young Native American Female.

Sinus of Valsalva aneurysm is a rare condition and associated with a high rate of mortality if rupture occurs. The aneurysms are rarely diagnosed until rupture occurs. This case describes a young Native American female whose only symptom was intermittent chest pain prior to the detection of the aneurysm along with a small ventricular septal defect.

Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the plus-maze test.

Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic receptors on performance in the plus-maze was studied in male rats bilaterally cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups that received either 1 microl injections of saline, (+/-)2-amino-7-phosphonoheptanoic acid (AP-7, 0.2, 0.

AP-7 into the nucleus accumbens disrupts acquisition but does not affect consolidation in a passive avoidance task.

The effect of the blockade of N-methyl-D-aspartic acid (NMDA)-type glutamatergic receptors in the nucleus accumbens septi (Acc) during different phases of a passive avoidance task (step-through paradigm, two chambers) of learning was studied in male rats which had been bilaterally cannulated into the Acc. Animals were trained with a punishment procedure (3 s shock of 1 mA) to avoid one of the chambers. The rats received either saline or (+/-)2-amino-7-phosphonoheptanoic acid (AP-7) solution (1 microg/1 microl) 10 min before training (pretraining schedule) or immediately after the shock (posttraining schedule).