Production of donor-derived sperm after spermatogonial stem cell transplantation in the dog.

Spermatogonial stem cell transplantation (SSCT) offers unique approaches to investigate SSC and to manipulate the male germline. We report here the first successful performance of this technique in the dog, which is an important model of human diseases. First, we investigated an irradiation protocol to deplete endogenous male germ cells in recipient testes.

Use of surgical hemoclips in radiation treatment planning.

The goal of this prospective study was to determine the effect of hemoclip use on the size of radiation treatment fields based on a 3-cm margin around a surgical incision alone (field setup 1) vs. a 3-cm margin around the surgical incision plus hemoclips (field setup 2). Forty-seven dogs that underwent surgical resection of a total of 55 soft tissue masses had surgical hemoclips placed at the time of surgery and orthogonal radiographs made immediately postoperatively.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I.

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human alpha-L-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of alpha-L-iduronidase-specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines.

Dietary n-3 polyunsaturated fatty acids enhance hormone ablation therapy in androgen-dependent prostate cancer.

Hormone ablation therapy typically causes regression of prostate cancer and represents an important means of treating this disease, particularly after metastasis. However, hormone therapy inevitably loses its effectiveness as tumors become androgen-independent, and this conversion often leads to death because of subsequent poor responses to other forms of treatment. Because environmental factors, such as diet, have been strongly linked to prostate cancer, we examined the affects of dietary polyunsaturated fatty acids (PUFAs; at 1.

A green tea component suppresses posttranslational expression of basic fibroblast growth factor in colorectal cancer.

Background & Aims: Green tea catechins are known to have anticarcinogenic effects. Epigallocatechin-3-gallate (EGCG) accounts for almost 50% of the total catechin content in green tea extract and has very potent antioxidant effects. EGCG also inhibits angiogenesis, possibly through the inhibition of proangiogenic factors including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which in turn, inhibits tumor growth and metastasis.

Optimization of region of interest luminances may enhance radiologists' light adaptation.

Rationale And Objectives: Radiologic image details are best discriminated at luminance levels to which the eye is adapted. Recommendations that ambient light conditions are matched to overall monitor luminance to encourage appropriate adaptation are based on an assumption that clinically significant regions within the image match average monitor luminance. The current work examines this assumption.

The impact of acoustic noise found within clinical departments on radiology performance.

Rationale And Objectives: In recent years, there has been increasing interest in the impact of environmental factors such as ambient light on radiologist performance. One commonly encountered distractor found within all clinical departments that has received little or no attention is acoustic noise.

Materials And Methods: The present work records the level of noises encountered within environments where radiologic images are viewed and establishes the impact of a clinically relevant level of noise on the ability of radiologists to perform a typical diagnostic task.

Portal radiography in veterinary radiation oncology: options and considerations.

Portal radiography involves the acquisition of images to visualize radiation treatment field(s) using the radiation treatment source. The standard has been the use of film-based systems with improvements over the years in film-screen technology providing near diagnostic quality images. More recent advances have included the development of digital systems with such notable improvements including ability to window/level images to enhance viewing and readability, and significant shortening of the time required to acquire images.

Discovery of ADDL--targeting small molecule drugs for Alzheimer's disease.

Amyloid beta-derived diffusible ligands (ADDLs) comprise the neurotoxic subset of soluble Abeta(1-42) oligomers, now widely considered to be the molecular cause of memory malfunction and neurodegeneration in Alzheimer's disease (AD). We have developed a screening cascade which identifies small molecule modulators of ADDL-mediated neurotoxicity. The primary screen involves a fluorescence resonance energy transfer (FRET)-based assay which selects inhibitors of Abeta1-42 oligomer assembly.

Comparison of 3 protocols for treatment after induction of remission in dogs with lymphoma.

Background: The optimal treatment after inducing complete remission (CR) in dogs with lymphoma has not been established.

Hypothesis: After inducing CR with L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisone (L-CHOP); consolidation with either half-body radiation therapy (HBRT); or lomustine (CCNU) and mechlorethamine, vincristine, procarbazine, prednisone (MOPP) would improve first remission duration compared with continuing a CHOP-based protocol for an additional 4 months.

Animals: Dogs with stage III-V lymphoma.

Adiposity-related protection of intestinal tumorigenesis: interaction with dietary calcium.

Although high-calcium diets have been reported to reduce the risk of colorectal cancer, our preliminary data with the adenomatous polyposis coli (Apc) Min mutation (Min/+;Apc(Min/+)) mouse shows a paradoxical increase in intestinal tumor loads (> 65%) with high calcium diets. Since we previously demonstrated that increasing dietary calcium reduces adiposity, and Apc(Min/+) mice on high calcium diets exhibited profound loss of adipose tissue, we hypothesized that loss of an adipose tissue-derived tumor suppressor factor(s) resulted in increased tumor susceptibility in animals on the high calcium diet. Accordingly, tumor prone Apc(Min/+) mice were crossed with obesity prone lethal yellow agouti (A(y)/a) mice to generate obese A(y)/Apc(Min/+) mice.

Intrathecal enzyme replacement therapy: successful treatment of brain disease via the cerebrospinal fluid.

Treatment of brain disease with recombinant proteins is difficult due to the blood-brain barrier. As an alternative to direct injections into the brain, we studied whether application of high concentrations of therapeutic enzymes via intrathecal (IT) injections could successfully drive uptake across the ependyma to treat brain disease. We studied IT enzyme replacement therapy with recombinant human iduronidase (rhIDU) in canine mucopolysaccharidosis I (MPS I, Hurler syndrome), a lysosomal storage disorder with brain and meningeal involvement.

Ambient lighting: effect of illumination on soft-copy viewing of radiographs of the wrist.

Objective: The aim of the work was to establish optimum ambient light conditions for viewing radiologic images of the wrist on liquid crystal display monitors.

Materials And Methods: Five ambient light levels were investigated: 480, 100, 40, 25, and 7 lux. Seventy-nine experienced radiologists were asked to examine 30 posteroanterior wrist images and decide whether a fracture was present.

Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing cats.

Intravenously administered docetaxel (DT) is problematic in cats because of the requirement for premedication to ameliorate acute vehicle-induced hypersensitivity reactions. Previously we have revealed that therapeutic plasma concentrations of DT can be achieved in normal and tumor-bearing dogs when DT is administered PO in combination with oral cyclosporin A (CSA). The purpose of this study was to identify the maximally tolerated dosage and characterize the pharmacokinetic disposition of oral DT combined with CSA in cats with tumors.

Nonsteroidal anti-inflammatory drug-activated gene-1 over expression in transgenic mice suppresses intestinal neoplasia.

Background & Aims: The nonsteroidal anti-inflammatory drug-activated gene (NAG-1) was identified as a proapoptotic, antitumorigenic protein in vitro, induced by many antitumorigenic and chemopreventive drugs including cyclooxygenase inhibitors. However, its antitumorigenic activity has not been elucidated in vivo.

Methods: Transgenic mice were generated that ubiquitously overexpress human NAG-1 under the control of a chicken beta-actin promoter (CAG).

Phenotypic characterization of polygenic type 2 diabetes in TALLYHO/JngJ mice.

The TALLYHO/JngJ (TH) strain is a newly established, polygenic mouse model for type 2 diabetes (T2D) and obesity, and we have previously reported some key physiological features of this model after the overt onset of diabetes. In the present work, we conducted a comprehensive phenotypic characterization of TH in order to completely characterize this new and relevant model for human T2D and obesity. We monitored the development of obesity and diabetes starting at 4 weeks of age by measuring body weight, glucose tolerance, and plasma levels of insulin, glucose, and triglyceride.

Sodium iodide I 131 treatment of dogs with nonresectable thyroid tumors: 39 cases (1990-2003).

Objective: To determine outcome for dogs with nonresectable thyroid carcinomas treated with sodium iodide I 131 and identify factors associated with outcome.

Design: Retrospective case series. Animals-39 dogs.

Phase I and pharmacokinetic evaluation of the combination of orally administered docetaxel and cyclosporin A in tumor-bearing dogs.

Objective: To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors.

Animals: 16 client-owned dogs with metastatic or advanced-stage refractory tumors.

Procedures: An open-label, dose-escalation, single-dose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted.

Evaluation of strontium 90 irradiation in treatment of cutaneous mast cell tumors in cats: 35 cases (1992-2002).

Objective: To determine the efficacy of strontium 90 beta irradiation in the management of cutaneous mast cell tumors (CMCTs) in cats.

Study Design: Retrospective case series.

Animals: 35 client-owned cats with CMCTs.

Veterinary radiation therapy: review and current state of the art.

Veterinary radiation oncology became a recognized specialty in 1994. Radiation therapy is an important component of a multimodality approach to treating cancer in companion animals. It is important to understand the many aspects of radiation, including the equipment used in external beam radiation therapy, the basic mechanism of action of ionizing radiation, the results of irradiating various histopathological types of tumors, as well as the associated potential acute and late side effects of radiation.

Recipient preparation and mixed germ cell isolation for spermatogonial stem cell transplantation in domestic cats.

The loss of genetic diversity poses a serious threat to the conservation of endangered species, including wild felids. We are attempting to develop spermatogonial stem cell transplantation in the cat as a tool to preserve and propagate male germ-plasm from genetically valuable animals, be they threatened wild species or lines of cats used as models for inherited diseases. In this study, we investigated the use of local external beam radiation treatment to deplete the endogenous germ cells of male domestic cats, a step necessary to prepare them for use as recipients for transplantation.

Suppression of tumor cell invasion by cyclooxygenase inhibitors is mediated by thrombospondin-1 via the early growth response gene Egr-1.

Cyclooxygenase (COX) inhibitors have antitumorigenic activity and increase the expression of the early growth response gene Egr-1, a tumor suppressor gene and transcription factor. In this study, we have investigated the gene regulatory and anti-invasive activity of two traditional nonsteroidal anti-inflammatory drugs (NSAID), sulindac sulfide and indomethacin. These compounds inhibited tumor cell invasion and induced Egr-1 expression in lung adenocarcinoma A549 cells.

Dietary (n-6) PUFA and intestinal tumorigenesis.

Cancer is the second leading cause of death in the United States, and mortality due to colorectal cancer is only surpassed by lung cancer. Epidemiological studies demonstrate that dietary polyunsaturated fats can have a profound effect on colorectal cancer risk. Experimental data indicate that modulation of cellular (n-6) PUFA metabolism can affect the progression of the disease.

A survey of veterinary radiation facilities in the United States during 2001.

A survey of veterinary radiation therapy facilities in the United States was done in 2001 to determine the type of equipment available, radiation protocols used, case load, tumor types irradiated, as well as other details of the practice of radiation oncology. A total of 42 sites were identified and included 17 (40%) academic institutions, and 25 (60%) private practice external beam radiation facilities. The overall response rate was 79% (33/42 responded).

Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges.