Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors.

Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood-brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment.

spp. aggregate and encyst on contact lens material increasing resistance to disinfection.

Introduction: keratitis is often caused when contaminate contact lenses and infect the cornea. is pervasive in the environment as a motile, foraging trophozoite or biocide-resistant and persistent cyst. As contact lens contamination is a potential first step in infection, we studied behavior and interactions on different contact lens materials.

Case Report: MRI, Clinical, and Pathological Correlates of Bromethalin Toxicosis in Three Dogs.

Bromethalin toxicosis is an increasingly common clinical presentation in dogs that may be fatal depending on the extent of intoxication. Antemortem diagnosis of bromethalin toxicosis was achieved in three dogs by demonstration of the active metabolite desmethylbromethalin in fat or serum. Magnetic resonance imaging (MRI) findings were consistent with a diffuse leukoencephalopathy with restricted diffusion and prominent involvement of the corticospinal motor tracts on T2-weighted and diffusion-weighted sequences.

Role of Cross-Sectional Imaging in Pediatric Interventional Cardiac Catheterization.

Management of congenital heart disease (CHD) has recently increased utilization of cross-sectional imaging to plan percutaneous interventions. Cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) imaging have become indispensable tools for pre-procedural planning prior to intervention in the pediatric cardiac catheterization lab. In this article, we review several common indications for referral and the impact of cross-sectional imaging on procedural planning, success, and patient surveillance.

Antimicrobial Efficacy of Contact Lens Solutions Assessed by ISO Standards.

Microbial keratitis (MK) is an eye infection caused by opportunistic bacteria or fungi, which may lead to sight-threatening corneal ulcers. These microorganisms can be introduced to the eye via improper contact lens usage or hygiene, or ineffective multipurpose solutions (MPSs) to disinfect daily wear contact lenses. Thus, the patient's choice and use of these MPSs is a known risk factor for the development of MK.

Fick versus flow: a real-time invasive cardiovascular magnetic resonance (iCMR) reproducibility study.

Background: Cardiac catheterization and cardiovascular magnetic resonance (CMR) imaging have distinct diagnostic roles in the congenital heart disease (CHD) population. Invasive CMR (iCMR) allows for a more thorough assessment of cardiac hemodynamics at the same time under the same conditions. It is assumed but not proven that iCMR gives an incremental value by providing more accurate flow quantification.

Patient-reported outcome measures for acne: a mixed-methods validation study (acne PROMs).

Objectives: To examine the acceptability and validity of two patient-reported outcome measures (PROMs) for adult acne, comparing them to the validated Acne-specific Quality of Life (Acne-QoL) measure.

Design: Mixed-methods validation study.

Setting: Participants were recruited by (1) mail-out through primary care if they had ever consulted for acne and received a prescription for acne treatment within the last 6 months, (2) opportunistically in secondary care and (3) poster advertisement in community venues.

Klf5 acetylation regulates luminal differentiation of basal progenitors in prostate development and regeneration.

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5.

CINP is a novel cofactor of KLF5 required for its role in the promotion of cell proliferation, survival and tumor growth.

Krüppel-like factor 5 (KLF5) both suppresses and promotes tumor growth depending on cellular context. The mechanisms underlying tumor promotion could be targetable for therapy. Although a number of transcriptional targets of KLF5 have been identified and implicated in KLF5-mediated tumor growth, how KLF5 regulates these genes remains to be addressed.

TTK promotes mesenchymal signaling via multiple mechanisms in triple negative breast cancer.

Abnormal expression of TTK kinase has been associated with the initiation, progression, and therapeutic resistance of breast and other cancers, but its roles remain to be clarified. In this study, we examined the role of TTK in triple negative breast cancer (TNBC), and found that higher TTK expression correlated with mesenchymal and proliferative phenotypes in TNBC cells. Pharmacologic inhibition and genomic silencing of TTK not only reversed the epithelial-to-mesenchymal transition (EMT) in TNBC cells, but also increased the expression of KLF5, an effector of TGF-β signaling and inhibitor of EMT.

HDAC-mediated deacetylation of KLF5 associates with its proteasomal degradation.

Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145.

Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors.

Background: The expression of the urokinase plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA), have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis.

ERRF sensitizes ERBB2-positive breast cancer cells to lapatinib treatment likely by attenuating MCL1 and ERBB2 expression.

Previously we found that the estrogen receptor (ER) related factor ERRF regulates cell proliferation and tumor growth, and its expression is positively associated with ER status and better survival but inversely associated with ERBB2 (also named HER2) status in breast cancer. Here we report that ERRF also plays an important role in the response of ERBB2-positive breast cancer cells to lapatinib, a dual tyrosine kinase inhibitor that interrupts the ERBB2 and EGFR pathway. In ERBB2-positive breast cancer cell lines, lower levels of ERRF expression correlated with lapatinib resistance, restoration of ERRF expression in lapatinib-resistant cell lines JIMT-1 and MDA-MB-453 enhanced their lapatinib responses, and knockdown of ERRF in lapatinib sensitive cell lines BT-474 and SK-BR-3 caused lapatinib resistance.

Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells.

Centrosome amplification (CA) amongst particular breast cancer subtypes (Her2+ subtype) is associated with genomic instability and aggressive tumor phenotypes. However, changes in signaling pathways associated with centrosome biology have not been fully explored in subtype specific models. Novel centrosome regulatory genes that are selectively altered in Her2+ breast cancer cells are of interest in discerning why CA is more prevalent in this subtype.

Coping and its effects on cancer caregiving.

Purpose: Various studies have documented the emotional distress family members of persons with cancer experience, and descriptive research has identified those psychosocial factors that protect cancer caregivers from a range of negative outcomes. The objective of this study was to determine how different coping strategies were associated with multiple domains of stress and negative health outcomes among cancer family caregivers.

Methods: A cross-sectional, correlational study design was used.