Dosimetry of Continuous Random Motion in High Dose Rate Strontium-90 Plesiotherapy.

Strontium-90 plesiotherapy delivers high doses of radiation to superficial lesions (<3 mm depth) with excellent sparing of deeper tissues. The sealed-source applicator tip is circular and 8-10 mm in diameter. Larger treatment fields are treated with multiple overlapping fields.

Outcomes associated with local treatment of nasal planum squamous cell carcinoma in dogs: 89 cases (2003-2020).

Objective: To describe the clinical characteristics, treatments, complications, and outcomes in dogs with nasal planum squamous cell carcinoma (SCC) undergoing local treatment.

Methods: A retrospective, multi-institutional study was performed. Medical records were searched to identify dogs diagnosed with nasal planum SCC.

Tumor-Localized Interleukin-2 and Interleukin-12 Combine with Radiation Therapy to Safely Potentiate Regression of Advanced Malignant Melanoma in Pet Dogs.

Purpose: Cytokines IL2 and IL12 exhibit potent anticancer activity but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability to bind and associate with tumor collagen after intratumoral injection potentiated response without toxicity in mice and was previously safe in pet dogs with sarcoma. Here, we sought to test the efficacy of this approach in dogs with advanced melanoma.

Targeting glioblastoma tumor hyaluronan to enhance therapeutic interventions that regulate metabolic cell properties.

Unlabelled: Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling.

Phase I evaluation of CycloSam (Sm-153-DOTMP) bone seeking radiopharmaceutical in dogs with spontaneous appendicular osteosarcoma.

Sm-DOTMP (CycloSam ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression.

Canine thyroid carcinomas: A review with emphasis on comparing the compact subtype of follicular thyroid carcinomas and medullary thyroid carcinomas.

Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas.

Combining radiation therapy with zoledronate for the treatment of osteo-invasive feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is the most common oral tumour diagnosed in pet cats and carries a poor prognosis with <10% one-year survival despite multi-modal therapies. Tumours of the mandible or maxilla are frequently osteo-invasive and pain can result from osteolysis. Zoledronate is a bisphosphonate that inhibits osteoclasts and reduces bone resorption.

Utilizing feline oral squamous cell carcinoma patients to develop NQO1-targeted therapy.

Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules.

Cytotoxicity of Cultured Canine Primary Hepatocytes Exposed to Itraconazole Is Decreased by Pre-treatment With Glutathione.

To identify the effect of glutathione (GSH) on cell survival in a novel model of itraconazole (ITZ)-associated hepatotoxicity using canine primary hepatocytes. Commercially sourced, cryopreserved male dog (Beagle) primary hepatocytes from a single donor. Using a sandwich culture technique, canine primary hepatocytes were exposed to serial dilutions of ITZ.

Physical Properties of Nanoparticles That Result in Improved Cancer Targeting.

The therapeutic efficacy of drugs is dependent upon the ability of a drug to reach its target, and drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure. Chemotherapy is the most common systemic treatment for cancer but can cause undesirable adverse effects, including toxicity to the bone marrow and gastrointestinal system. Therefore, nanotechnology-based drug delivery systems have been developed to reduce the adverse effects of traditional chemotherapy by enhancing the penetration and selective drug retention in tumor tissues.

Medulloblastoma in a 6 Year Old Mixed Breed Dog: Surgical Debulking and Chemotherapy.

A medulloblastoma was surgically debulked from a 6 year old American Staffordshire Terrier, who then received a modified lomustine (CCNU), vincristine, procarbazine, and prednisolone (LOPP) protocol. The dog improved significantly and continued to do well until deterioration and euthanasia 5 months following surgery. This is the first known published case report of surgical cytoreductive surgery of a medulloblastoma in a dog with documented response to surgery and chemotherapy.

A comparison of risk factors for metastasis at diagnosis in humans and dogs with osteosarcoma.

Background: Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease.

Methods: This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program.

Use of computed tomography and radiation therapy planning software to develop a novel formula for body surface area calculation in dogs.

Background: Body surface area (BSA) can reflect metabolic rate that might normalize dosing of chemotherapeutics across widely variable weights within a species. The current BSA formula for dogs lacks height, length, and body condition.

Hypothesis: Computed tomography (CT) imaging will allow inclusion of morphometric variables in allometric modeling of BSA in dogs resulting in an improved formula for BSA estimation.

Evaluation of intravenous and subcutaneous administration of a novel, excipient-free, nanoparticulate formulation of paclitaxel in dogs with spontaneously occurring neoplasia.

Carriers used to solubilize taxane chemotherapy drugs cause severe hypersensitivity. Nanoparticle formulations can provide improved dissolution and bioavailability of taxanes. Thus, a nanoparticulate, excipient-free formulation of paclitaxel (CTI52010) was evaluated in tumour-bearing dogs with intravenous and subcutaneous delivery.

The effect of diet on serum 25-hydroxyvitamin D concentrations in dogs.

Background: Vitamin D (vitD) deficiency is linked to many disease states including rickets and cancer, and vitD supplementation to improve response to cancer therapy has been explored. Supplementation may be most appropriate for dogs with suboptimal vitD concentrations. In dogs, the primary source of vitD is diet (predominantly via commercial dog food).

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer.

Introduction: Gum arabic-coated radioactive gold nanoparticles (GA-(198)AuNPs) offer several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-(198)AuNPs injected intralesionally. We proposed that a single treatment of GA-(198)AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity.

Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines.

Background: Paclitaxel is an effective antimitotic agent in cancer treatment; however, one of its most common toxicities is hypersensitivity due to excipients used for water solubility. Nanoparticulate paclitaxel (Crititax®, CTI52010) is paclitaxel that consists only of nanoparticulate drug in saline. Our objective was to examine the effect of nanoparticulate paclitaxel on prostate cancer cells derived from castration-resistant prostate cancer in men and dogs, as companion dogs represent a unique naturally occurring model of castration-resistant prostate cancer.

Evaluation of fixation time using Diff-Quik for staining of canine mast cell tumor aspirates.

Background: Mast cell tumors are the most common cutaneous tumor in the dog and are often diagnosed via fine-needle aspiration and cytology. Many veterinary practices use Diff-Quik stain for these cases because it is easy to use and provides rapid results. Anecdotal reports suggest that Diff-Quik does not stain mast cell tumor granules well and that increased duration of fixation time can improve staining quality; however, this has not been prospectively evaluated.

Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs.

Background: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs.

Reirradiation of recurrent canine nasal tumors.

Canine nasal tumors are typically treated with radiation therapy but most patients develop local recurrence. Our purpose was to evaluate tumor and normal tissue response to reirradiation in nine dogs. The median dose delivered with the first protocol was 50 Gy (range 44-55 Gy) and the median fraction number was 18 (range 15-20).

Evaluation of factors associated with second remission in dogs with lymphoma undergoing retreatment with a cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol: 95 cases (2000-2007).

Objective: To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol.

Design: Retrospective case series.

Animals: 95 dogs with lymphoma.

Targeted combined aerosol chemotherapy in dogs and radiologic toxicity grading.

Background: We investigated whether combination chemotherapy, targeted with the AeroProbe® Intracorporeal Nebulizing Catheter (INC), could be safely administered, and developed a radiologic grading scheme to monitor subclinical effects on the lungs.

Methods: In anesthetized and mechanically ventilated healthy dogs (n = 3), we introduced the INC via a flexible bronchoscope into the right caudal lung lobe and administered escalating dosages of gemcitabine (1, 2, 3, or 6 mg/kg) followed by cisplatin (10 mg/m(2)). Treatments were performed every 2 weeks for 4 treatments and dogs were monitored weekly with physical examination, biochemical tests, and thoracic radiographs.