Vet. Sci.2015, 2(4), 423-439; doi:10.3390/vetsci2040423 (registering DOI) - published 1 December 2015 Show/Hide Abstract
Abstract: Over the last one to two decades, the field of cancer immunotherapy has rapidly progressed from early preclinical studies to a successful clinical reality and fourth major pillar of human cancer therapy. While current excitement in the field of immunotherapy is being driven by several major breakthroughs including immune checkpoint inhibitors and adoptive cell therapies, these advances stem from a foundation of pivotal studies demonstrating the immune systems role in tumor control and eradication. The following will be a succinct review on veterinary cancer immunotherapy as it pertains to manipulation of the innate immune system to control tumor growth and metastasis. In addition, we will provide an update on recent progress in our understanding of the innate immune system in veterinary tumor immunology, and how these gains may lead to novel therapies for the treatment of cancer in companion animals.
Abstract: Mercury (Hg) is a ubiquitous global contaminant with important public health implications. Mercury is released from a variety of anthropogenic, industrial processes, enters the earth's atmosphere and is re-deposited onto the earth’s surface in rainfall. Much of this Hg enters the oceans which cover the majority of the earth’s surface. In the marine environment, inorganic Hg is converted to the most toxic form of the element, methylmercury, and biomagnified through the trophic levels of the food web. The bottlenose dolphin (Tursiops truncatus) is the apex predator in many estuarine and coastal ecosystems. Due to their long life span and trophic position, bottlenose dolphins bioaccumulate high concentrations of contaminants including Hg, thus making them an important sentinel species for ecosystem and public health. Bottlenose dolphins in Florida bioaccumulate high concentrations of Hg in their blood, skin and internal organs. The concentrations of Hg in blood and skin of bottlenose dolphins of the Indian River Lagoon, FL (IRL) are among the highest reported world-wide. In previous studies, we demonstrated associations between concentrations of total Hg in the blood and skin of IRL dolphins and markers of endocrine, renal, hepatic, hematologic and immune system dysfunction. The predominant manifestation of exposure to mercury in humans is neurotoxicity. During the 1950s and 1960s, residents of Minamata bay, Japan were exposed to high concentrations of methyl mercury as the result of ingestion of fish and shellfish that had become contaminated in this infamous environmental disaster. Affected adults had severe motor and sensory abnormalities often leading to death. Methyl mercury crosses the placenta during pregnancy. Children exposed in utero were born with multiple congenital anomalies and also suffered from neurologic disorders. Significantly, local cats that consumed Hg contaminated fish developed severe signs of neurotoxicity which led to their subsequent description as the “dancing cats of Minamata bay”. Unfortunately, the cause of these strange manifestations in cats was not recognized in time to prevent hundreds of additional cases from occurring. More recent studies have shown that exposure to mercury as a result of seafood consumption during pregnancy may result in multiple cognitive and neurodevelopmental effects in children. The levels of mercury found in bottlenose dolphins and the health effects we identified alerted us to the possibility of an important public health hazard. The IRL occupies 40 percent of the east coast of Florida and is bordered by counties with approximately 2.5 million human inhabitants. Therefore, we hypothesized that local inhabitants in communities bordering the IRL could be at risk of exposure to Hg from the consumption of fish and shellfish. We measured hair Hg in 135 local residents and found a mean concentration of 1.53 µg/g which was higher than that from previous studies of sport fishermen and coastal residents in other states. Over 50% of participants had a hair Hg concentration which exceeded the U.S. EPA exposure guideline. Hair Hg concentration was directly related to the frequency of seafood consumption and to the proportion of fish and shellfish obtained from local recreational sources. This study clearly exemplifies the importance of an animal sentinel in identifying a public health hazard and is virtually unique in “closing the loop” between animal and human health.
Abstract: Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous masses are often treatable by tumor excision, visceral tumors are almost always incurable. Treatment advances for this disease have been limited due to a poor understanding of the overall tumor biology. Based upon its histological appearance, HSA has been presumed to originate from transformed endothelial cells; however, accumulating data now suggest a pluripotent bone marrow progenitor as the cell of origin for this disease. More recently, the identification of a novel subclassification of HSAs has provided a foundation to further our understanding of the cellular characteristics of HSA tumor cells, along with those of the cells comprising the tumor microenvironment. These discoveries hold promise for the development of new approaches to improve treatments for canine HSA, as well as to establish the utility of this disease as a spontaneous model to understand the pathogenesis and develop new treatments for vascular tumors of humans. In this review, we will provide a brief historical perspective and pathobiology of canine HSA, along with a focus on the recent advances in the molecular and cellular understanding of these tumors. In addition, future directions that should continue to improve our understanding of HSA pathogenesis will be discussed.
Abstract: Harnessing the ability of the immune system to eradicate cancer has been a long-held goal of oncology. Work from the last two decades has finally brought immunotherapy into the forefront for cancer treatment, with demonstrable clinical success for aggressive tumors where other therapies had failed. In this review, we will discuss a range of therapies that are in different stages of clinical or preclinical development for companion animals with cancer, and which share the common objective of eliciting adaptive, anti-tumor immune responses. Even though challenges remain, manipulating the immune system holds significant promise to create durable responses and improve outcomes in companion animals with cancer. Furthermore, what we learn from this process will inform and accelerate development of comparable therapies for human cancer patients.
Abstract: We examined 185 metabolites in 30 adult Humboldt Penguins (Spheniscus humboldti) nesting at the Punta San Juan Marine Protected Area, Peru, in order to examine gender differences in metabolome profiles, particularly those involved in metabolism and energetics. The majority of the compounds identified were fatty (26% of total identified compounds), organic (19%), and amino (16%) acids. We were able to differentiate male and female penguins with 96.6% accuracy on the basis of 12 metabolites, most of which are involved in lipid and carbohydrate metabolism. These included 2-oxoglutarate, erythronic acid, GABA, mannitol, sedoheptulose 7-phosphate, and serine and six metabolites present in higher concentrations in females compared to males (2-aminoadipic acid, O-phosphorylethanolamine, glycerol 2-phosphate, glycerol 3-phosphate, pantothenic acid, and creatinine). Of these, 2-oxoglutarate and glycerol 3-phosphate were key metabolites distinguishing gender. Our results indicated that male and female Humboldt Penguins were characterized by differing metabolic states. Such differences could be important to individual and brood survival in times of environmental stress.