Tumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.

High-frequency irreversible electroporation (H-FIRE), a nonthermal brain tumor ablation therapeutic, generates a central tumor ablation zone while transiently disrupting the peritumoral blood-brain barrier (BBB). We hypothesized that bystander effects of H-FIRE tumor cell ablation, mediated by small tumor-derived extracellular vesicles (sTDEV), disrupt the BBB endothelium. Monolayers of bEnd.

Development of non-pulmonary soft-tissue metastasis is not a poor prognostic indicator in dogs with metastatic appendicular osteosarcoma.

Objectives: To evaluate whether patient factors affect development of non-pulmonary soft-tissue metastases following treatment of canine appendicular osteosarcoma and to report and compare outcomes to those in dogs with pulmonary or osseous metastases.

Animals And Procedure: The records of 3 veterinary teaching hospitals were reviewed to identify dogs that received definitive treatment for a primary appendicular osteosarcoma lesion and chemotherapy between January 2010 and June 2022. Dogs with non-pulmonary metastases following initial treatment were included.

Exploring Canine Mammary Cancer through Liquid Biopsy: Proteomic Profiling of Small Extracellular Vesicles.

(Background). Canine mammary tumors (CMTs) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients.

Outcome in dogs with invasive adrenal gland tumors that did not pursue adrenalectomy.

Objective: To report the survival times in dogs diagnosed with adrenal tumors with vascular or soft tissue invasion that did not undergo adrenalectomy.

Animals: Retrospective case series of 32 client-owned dogs.

Methods: The medical records of a referral veterinary hospital were reviewed to identify dogs that were diagnosed with an invasive adrenal mass and did not undergo adrenalectomy between January 2013 and December 2022.

Retrospective Evaluation of Melphalan, Vincristine, and Cytarabine Chemotherapy for the Treatment of Relapsed Canine Lymphoma.

Dogs diagnosed with multicentric lymphoma often relapse following induction therapy within the first year of treatment. The primary aim of this study was to evaluate the tolerability of a novel drug combination using melphalan, vincristine, and cytarabine (MOC) for the treatment of relapsed lymphoma. On day 1, dogs were treated with vincristine (0.

Top-down mass spectrometry for characterizing the low molecular weight proteome of canine osteosarcoma cell phenotypes.

Osteosarcoma (OS) is the most common primary malignant tumor of bone, which occupying about 20% of all bone cancers. To increase understanding of the biology of OS, we developed and evaluated a top-down mass spectrometry approach to detect, identify and quantify low molecular weight (MW) proteins (i.e.

Potential Promises and Perils of Human Biological Treatments for Immunotherapy in Veterinary Oncology.

The emergence of immunotherapy for the treatment of human cancers has heralded a new era in oncology, one that is making its way into the veterinary clinic. As the immune system of many animal species commonly seen by veterinarians is similar to humans, there is great hope for the translation of human therapies into veterinary oncology. The simplest approach for veterinarians would be to adopt existing reagents that have been developed for human medicine, due to the potential of reduced cost and the time it takes to develop a new drug.

Cellular Transcriptomics of Carboplatin Resistance in a Metastatic Canine Osteosarcoma Cell Line.

Osteosarcoma prognosis has remained unchanged for the past three decades. In both humans and canines, treatment is limited to excision, radiation, and chemotherapy. Chemoresistance is the primary cause of treatment failure, and the trajectory of tumor evolution while under selective pressure from treatment is thought to be the major contributing factor in both species.

Creating a Selective Nanobody Against 3-Nitrotyrosine Containing Proteins.

A critical step in developing therapeutics for oxidative stress-related pathologies is the ability to determine which specific modified protein species are innocuous by-products of pathology and which are causative agents. To achieve this goal, technologies are needed that can identify, characterize and quantify oxidative post translational modifications (oxPTMs). Nanobodies (Nbs) represent exquisite tools for intracellular tracking of molecules due to their small size, stability and engineerability.

Canine osteosarcoma cells exhibit basal accumulation of multiple chaperone proteins and are sensitive to small molecule inhibitors of GRP78 and heat shock protein function.

Osteosarcoma is the most common type of bone cancer in dogs and humans, with significant numbers of patients experiencing treatment failure and disease progression. In our search for new approaches to treat osteosarcoma, we previously detected multiple chaperone proteins in the surface-exposed proteome of canine osteosarcoma cells. In the present study, we characterized expression of representative chaperones and find evidence for stress adaptation in canine osteosarcoma cells relative to osteogenic progenitors from normal bone.

Wicking microfluidic approach to separate blood plasma from whole blood to facilitate downstream assays.

Separation of blood plasma or serum from blood is essential for accurate analysis. Conventional blood separation requires instrumentation, reagents, and large sample volumes, limiting this process to laboratory environments with trained personnel. Full implementation of effective blood separation and analysis on microliter sample volumes for point of care (POC) diagnostics has proven extremely challenging resulting in a growing market demand, with common challenges such as expensive device fabrication processes or devices being comprised of materials which are not easily disposable.

Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma.

Background: Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown to play a role in drug resistance, but a comprehensive protein signature relating to osteosarcoma carboplatin resistance has not been fully characterized.

Methods: In this study, cell lysates and exosomes from two derivatives (HMPOS-2.

Fasting reduces the incidence of vincristine-associated adverse events in dogs.

Fasting has been shown to decrease chemotherapy-associated adverse events (AEs), in part through insulin-like growth factor (IGF-1) reduction, and may induce a protective effect on normal cells during chemotherapy treatment in mice and people. The purpose of this study was to evaluate the effect of fasting on constitutional, bone marrow and gastrointestinal (GI) AEs, and serum glucose, IGF-1 and insulin levels in dogs receiving vincristine. The study was a prospective, crossover clinical trial in tumour-bearing dogs.

Prospective evaluation of the lymph node proteome in dogs with multicentric lymphoma supplemented with sulforaphane.

Background: Lymphoma (LSA) is a common malignancy in dogs. Epigenetic changes are linked to LSA pathogenesis and poor prognosis in humans, and LSA pathogenesis in dogs. Sulforaphane (SFN), an epigenetic-targeting compound, has recently gained interest in relation to cancer prevention and therapy.

Nanoparticle-Based Platform for Activatable Fluorescence Imaging and Photothermal Ablation of Endometriosis.

Endometriosis is a painful disorder where endometrium-like tissue forms lesions outside of the uterine cavity. Intraoperative identification and removal of these lesions are difficult. This study presents a nanoplatform that concurrently delineates and ablates endometriosis tissues using real-time near-infrared (NIR) fluorescence and photothermal therapy (PTT).

Nasal adenocarcinoma as a suspected secondary malignant neoplasm in a cat previously treated for nasal lymphoma.

Case Summary: A case of nasal adenocarcinoma as a suspected secondary malignant neoplasm following definitive radiation therapy and multiagent chemotherapy for nasal lymphoma is described. An 11-year-old spayed female domestic shorthair cat was presented for a 3-week history of progressive facial swelling located over the nasal planum and extending to the medial canthus of the right eye. The cat was previously diagnosed with nasal lymphoma and treated with chemotherapy and definitive radiation 2.

Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities.

Osteosarcoma (OS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. The proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined.

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy.

Purpose: To assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for in vivo localization and combinatorial phototherapy.

Materials And Methods: A VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery.

Long-term outcomes of dogs undergoing surgical resection of mast cell tumors and soft tissue sarcomas: A prospective 2-year-long study.

Objective: Report clinical outcomes of dogs with surgically excised mast cell tumors (MCT) and soft tissue sarcomas (STS).

Study Design: Prospective clinical study.

Sample Population: Fifty-three dogs with 52 MCT (50 low grade, 2 high grade) and 19 STS (12 grade I, 6 grade II, 1 grade III).

Autocrine production of reproductive axis neuropeptides affects proliferation of canine osteosarcoma in vitro.

Background: Osteosarcoma strikes hundreds of people each year, of both advanced and younger ages, and is often terminal. Like many tumor types, these bone tumors will frequently undergo a neuroendocrine transition, utilizing autocrine and/or paracrine hormones as growth factors and/or promoters of angiogenesis to facilitate progression and metastasis. While many of these factors and their actions on tumor growth are characterized, some tumor-derived neuropeptides remain unexplored.

Feasibility of near-infrared fluorescence imaging for sentinel lymph node evaluation of the oral cavity in healthy dogs.

OBJECTIVE To evaluate the usefulness of injection of indocyanine green (ICG) solution with near-infrared (NIR) fluorescence imaging for transcutaneous detection of sentinel lymph nodes (SLNs) and their associated lymphatic vessels in the oral mucosa of healthy dogs. ANIMALS 6 adult purpose-bred research hounds. PROCEDURES Each dog was sedated, and 1 mL of ICG solution was injected into the gingival mucosa dorsal to the right maxillary canine tooth.

Sulforaphane absorption and histone deacetylase activity following single dosing of broccoli sprout supplement in normal dogs.

The role of epigenetic alterations during cancer has gained increasing attention and has resulted in a paradigm shift in our understanding of mechanisms leading to cancer susceptibility. Sulforaphane (SFN) is a naturally occurring isothiocyanate derived from the precursor glucosinolate, glucoraphanin (GFN), which is found in cruciferous vegetables such as broccoli. Sulforaphane has been shown to suppress tumour growth by several mechanisms including inhibiting histone deacetylases.

A Preliminary Proteomic Investigation of Circulating Exosomes and Discovery of Biomarkers Associated with the Progression of Osteosarcoma in a Clinical Model of Spontaneous Disease.

Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease and can be found in blood. The exosomal proteomic cargo can often be traced to the cells from which they originated, reflecting the physiological status of these cells. The similarities between cancer exosomes and the tumor cells they originate from exhibit the potential of these vesicles as an invaluable target for liquid biopsies.

A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided Surgery and Combinatorial Phototherapy.

Fluorescence image-guided surgery combined with intraoperative therapeutic modalities has great potential for intraoperative detection of oncologic targets and eradication of unresectable cancer residues. Therefore, we have developed an activatable theranostic nanoplatform that can be used concurrently for two purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence signal during surgery, and (2) intraoperative targeted treatment to further eliminate unresected disease sites by non-toxic phototherapy. The developed nanoplatform is based on a single agent, silicon naphthalocyanine (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)--poly(ɛ-caprolactone)) nanoparticles.

Reductions in margin length after excision of grade II mast cell tumors and grade I and II soft tissue sarcomas in dogs.

Objective: Quantify changes in the circumferential lengths of surgical margins of resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the time of collection and histopathology.

Study Design: Prospective, hypothesis-driven, clinical study.

Sample Population: Two hundred and thirty-seven margins from 69 excised tumors (50 MCT and 19 STS) in 51 client-owned dogs.