Inhibition of EphA3 Expression in Tumour Stromal Cells Suppresses Tumour Growth and Progression.

Tumour progression relies on interactions with untransformed cells in the tumour microenvironment (TME), including cancer-associated fibroblasts (CAFs), which promote blood supply, tumour progression, and immune evasion. Eph receptor tyrosine kinases are cell guidance receptors that are most active during development but re-emerge in cancer and are recognised drug targets. EphA3 is overexpressed in a wide range of tumour types, and we previously found expression particularly in stromal and vascular tissues of the TME.

Cross-sectional characterization of renal function in cats with caudal stomatitis.

Objectives: The objective of the study was to compare renal functional biomarkers in cats and in caudal stomatitis (CS) and in age-matched control cats.

Methods: A cross-sectional, case-control study was conducted on 44 client-owned cats with CS that were prospectively enrolled and evaluated for a Comprehensive Oral Health Assessment and Treatment at one of four institutions. Renal function was assessed with measurement of serum creatinine, urea nitrogen, serum symmetric dimethylarginine, urinalysis, urine protein:creatinine ratio and urine protein electrophoresis.

The cellular and molecular mediators of metastasis to the lung.

Organ-specific metastasis to secondary organs is dependent on the formation of a supportive pre-metastatic niche. This tissue-specific microenvironmental response is thought to be mediated by mutational and epigenetic changes to primary tumour cells resulting in altered cross-talk between cell types. This response is augmented through the release of tumour and stromal signalling mediators including cytokines, chemokines, exosomes and growth factors.

Brain Vascular Microenvironments in Cancer Metastasis.

Primary tumours, particularly from major solid organs, are able to disseminate into the blood and lymphatic system and spread to distant sites. These secondary metastases to other major organs are the most lethal aspect of cancer, accounting for the majority of cancer deaths. The brain is a frequent site of metastasis, and brain metastases are often fatal due to the critical role of the nervous system and the limited options for treatment, including surgery.

The Interplay Between Lymphatic Vessels and Chemokines.

Chemokines are a family of small protein cytokines that act as chemoattractants to migrating cells, in particular those of the immune system. They are categorized functionally as either homeostatic, constitutively produced by tissues for basal levels of cell migration, or inflammatory, where they are generated in association with a pathological inflammatory response. While the extravasation of leukocytes via blood vessels is a key step in cells entering the tissues, the lymphatic vessels also serve as a conduit for cells that are recruited and localized through chemoattractant gradients.

CCL27/CCL28-CCR10 Chemokine Signaling Mediates Migration of Lymphatic Endothelial Cells.

Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new lymphatic vessels (lymphangiogenesis), or remodeling of existing lymphatics, is thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis.

Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling.

Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration.

A Three-Dimensional Lymphatic Endothelial Cell Tube Formation Assay to Identify Novel Kinases Involved in Lymphatic Vessel Remodeling.

The lymphatic system is a series of vessels that transport cells and excess fluid from tissues to the blood vascular system. Normally quiescent, the lymphatics can grow or remodel in response to developmental, immunological, or cells pathological stimuli. Lymphatic vessels comprise lymphatic endothelial cells (LECs) that can respond to external growth factors by undergoing proliferation, migration, adhesion, and tube and lumen formation into new vessel structures, a process known as lymphangiogenesis.

The Role of the Tumor Vasculature in the Host Immune Response: Implications for Therapeutic Strategies Targeting the Tumor Microenvironment.

Recently developed cancer immunotherapy approaches including immune checkpoint inhibitors and chimeric antigen receptor T cell transfer are showing promising results both in trials and in clinical practice. These approaches reflect increasing recognition of the crucial role of the tumor microenvironment in cancer development and progression. Cancer cells do not act alone, but develop a complex relationship with the environment in which they reside.

COMPUTED TOMOGRAPHY OF TOOTH RESORPTION IN CATS.

Tooth resorption is the most common dental disease in cats and can be a source of oral pain. The current clinical gold standard for diagnosis includes a combination of oral exam and dental radiography, however early lesions are not always detected. Computed tomography (CT) of the skull, including the dental arches, is a commonly performed diagnostic procedure, however the appearance of tooth resorption on CT and the diagnostic ability of CT to detect tooth resorption have not been evaluated.

Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that supports vascular growth.

Eph and ephrin proteins are essential cell guidance cues that orchestrate cell navigation and control cell-cell interactions during developmental tissue patterning, organogenesis and vasculogenesis. They have been extensively studied in animal models of embryogenesis and adult tissue regeneration, but less is known about their expression and function during human tissue and organ regeneration. We discovered the hypoxia inducible factor (HIF)-1α-controlled expression of EphA3, an Eph family member with critical functions during human tumour progression, in the vascularised tissue of regenerating human endometrium and on isolated human endometrial multipotent mesenchymal stromal cells (eMSCs), but not in other highly vascularised human organs.

EphA3 biology and cancer.

Eph receptor tyrosine kinases control cell-cell interactions during normal and oncogenic development, and are implicated in a range of processes including angiogenesis, stem cell maintenance and metastasis. They are thus of great interest as targets for cancer therapy. EphA3, originally isolated from leukemic and melanoma cells, is presently one of the most promising therapeutic targets, with multiple tumor-promoting roles in a variety of cancer types.

Ultrasound elastography of the liver, spleen, and kidneys in clinically normal cats.

A large amount of overlap exists in the B-mode ultrasound appearance of normal and abnormal liver, spleen, and kidney tissues in cats. Therefore, invasive tissue sampling procedures remain the standard method for diagnosing diseases in these organs. The purpose of our study was to assess the feasibility of ultrasound elastography as a technique for improving noninvasive characterization of the feline liver, spleen, and kidneys.

Vascular remodeling in cancer.

The growth and dissemination of tumors rely on an altered vascular network, which supports their survival and expansion and provides accessibility to the vasculature and a route of transport for metastasizing tumor cells. The remodeling of vascular structures through generation of new vessels (for example, via tumor angiogenesis) is a well studied, even if still quite poorly understood, process in human cancer. Antiangiogenic therapies have provided insight into the contribution of angiogenesis to the biology of human tumors, yet have also revealed the ease with which resistance to antiangiogenic drugs can develop, presumably involving alterations to vascular signaling mechanisms.

Signaling for lymphangiogenesis via VEGFR-3 is required for the early events of metastasis.

Metastasis to regional lymph nodes is an important and early event in many tumors. Vascular endothelial growth factor-C (VEGF-C), VEGF-D and their receptor VEGFR-3, play a role in tumor spread via the lymphatics, although the timing of their involvement is not understood. In contrast, VEGFR-2, activated by VEGF-A, VEGF-C and VEGF-D, is a mediator of angiogenesis and drives primary tumor growth.

Model development for determining the efficacy of a combination coating for the prevention of perioperative device related infections: a pilot study.

Antibiotic resistant bacterial infections are a growing problem in patient care. These infections are difficult to treat and severely affect the patient's quality of life. The goal of this translational experiment was to investigate the antimicrobial potential of cationic steroidal antimicrobial-13 (CSA-13) for the prevention of perioperative device-related infections in vivo.

The artiodactyl calcaneus as a potential 'control bone' cautions against simple interpretations of trabecular bone adaptation in the anthropoid femoral neck.

For over a century, the arched trabecular patterns of the human proximal femur have been considered to resemble tension and compression stress trajectories produced by stereotypical bending loads. This reflects conventional modeling of the human femoral neck-head region as a short cantilevered beam. Although this conception is the foundation of many biomechanical, clinical, paleontological, and comparative morphological studies of trabecular bone in various species, attempts have not been made to contrast these data to a bone that could be considered a 'control' for simple/stereotypical bending.

Effects of intratesticular injection of bupivacaine and epidural administration of morphine in dogs undergoing castration.

Objective: To determine the intraoperative and postoperative analgesic efficacy of intratesticular or epidural injection of analgesics for dogs undergoing castration.

Design: Randomized controlled trial.

Animals: 51 healthy male dogs.

Development of a broad spectrum polymer-released antimicrobial coating for the prevention of resistant strain bacterial infections.

More than 400,000 primary hip and knee replacement surgeries are performed each year in the United States. From these procedures, approximately 0.5-3% will become infected and when considering revision surgeries, this rate has been found to increase significantly.