Humans are not the only species to spontaneously develop metastatic cancer as cases of metastasis have been reported in a wide range of animals, including dinosaurs. Mouse models have been an invaluable tool in experimental and clinical metastasis research, with the use of genetically-engineered mouse models that spontaneously develop metastasis or ectopic/orthotopic transplantation of tumour cells to wildtype or immunodeficient mice being responsible for many key advances in our understanding of metastasis. However, are there other species that can also be relevant models? Similarities to humans in terms of environmental exposures, life-span, genetics, histopathology and available therapeutics are all factors that can be considered when looking at species other than the laboratory mouse. This review will explore the occurrence of metastasis in multiple species from a variety of domestic, captive and free-living veterinary cases to assist in identifying potential alternative experimental and clinical research models relevant to humans.

Amphibian pathogens are of current interest as contributors to the global decline of amphibians. However, compared with chytrid fungi and ranaviruses, herpesviruses have received relatively little attention. Two ranid herpesviruses have been described: namely, Ranid herpesvirus 1 (RHV1) and Ranid herpesvirus 2 (RHV2). This article describes the discovery and partial characterization of a novel virus tentatively named Ranid herpesvirus 3 (RHV3), a candidate member of the genus Batrachovirus in the family Alloherpesviridae. RHV3 infection in wild common frogs (Rana temporaria) was associated with severe multifocal epidermal hyperplasia, dermal edema, a minor inflammatory response, and variable mucous gland degeneration. Intranuclear inclusions were numerous in the affected epidermis together with unique extracellular aggregates of herpesvirus-like particles. The RHV3-associated skin disease has features similar to those of a condition recognized in European frogs for the last 20 years and whose cause has remained elusive. The genome of RHV3 shares most of the features of the Alloherpesviruses. The characterization of this presumptive pathogen may be of value for amphibian conservation and for a better understanding of the biology of Alloherpesviruses.

:  A series of eight cases of intestinal adenocarcinoma in Amazon milk frog (Trachycephalus resinifictrix) is described. All cases presented with signs of inappetence and weight loss, and evidence of large intestinal distention on gross postmortem, with six of the eight cases showing a grossly visible large intestinal mass. Histologic examination identified the mass as an intestinal adenocarcinoma in all cases. No specific etiologic agent could be identified. This is the first report of neoplasia in the Amazon milk frog, and the first reported series of amphibian gastrointestinal neoplasia.

Owing to the alluring possibility of contactless temperature probing with microscopic spatial resolution, photoluminescence nanothermometry at the nanoscale is rapidly advancing towards its successful application in biomedical sciences. The emergence of near-infrared nanothermometers has paved the way for temperature sensing at the deep tissue level. However, water dispersibility, adequate size at the nanoscale, and the capability to efficiently operate in the second and third biological optical transparency windows are the requirements that still have to be fulfilled in a single nanoprobe. In this work, these requirements are addressed by rare-earth doped nanoparticles with core/shell-architecture, dispersed in water, whose excitation and emission wavelengths conveniently fall within the biological optical transparency windows. Under heating-free 800 nm excitation, double nanothermometry is realized either with Ho³⁺-Nd³⁺ (1.18-1.34 μm) or Er³⁺-Nd³⁺ (1.55-1.34 μm) NIR emission band ratios, both displaying equal thermal sensitivities around 1.1% °C^-1. It is further demonstrated that, along with the interionic energy transfer processes, the thermometric properties of these nanoparticles are also governed by the temperature dependent energy transfer to the surrounding solvent (water) molecules. Overall, this work presents a novel water dispersible double ratiometric nanothermometer operating in the second and third biological optical transparency windows. The temperature dependent particle-solvent interaction is also presented, which is critical for e.g. future in vivo applications.

The order Herpesvirales encompasses viruses that share structural, genetic, and biological properties. However, members of this order infect hosts ranging from molluscs to humans. It is currently divided into three phylogenetically related families. The Alloherpesviridae family contains viruses infecting fish and amphibians. There are 12 alloherpesviruses described to date, 10 of which infect fish. Over the last decade, cyprinid herpesvirus 3 (CyHV-3) infecting common and koi carp has emerged as the archetype of fish alloherpesviruses. Since its first description in the late 1990s, this virus has induced important economic losses in common and koi carp worldwide. It has also had negative environmental implications by affecting wild carp populations. These negative impacts and the importance of the host species have stimulated studies aimed at developing diagnostic and prophylactic tools. Unexpectedly, the data generated by these applied studies have stimulated interest in CyHV-3 as a model for fundamental research. This review intends to provide a complete overview of the knowledge currently available on CyHV-3.

This article provides a broad overview of the field of inappropriate gene expression in many organisms across the animal and plant kingdoms as well as its importance to human disease in general and cancer in particular. Study of the topic is especially important for understanding how the chaotic maelstrom of evolving and cascading regulatory genetic interactions in an advancing cancer produces its clinical effects and for designing pragmatic solutions to how such disorder might eventually be tamed. It is emphasized that the topic warrants much more attention in research and in clinical practice because of the added value it brings to refining cancer diagnosis and treatment and to the assessment of prognostic markers. It is also particularly relevant to understanding the etiology and extensive clinical manifestations of paraneoplastic syndromes affecting multiple organs remote from the tumor and the treatment or amelioration of the substantial morbidity that they cause in cancer patients. More broadly, inappropriate expression can be caused by a number of mechanisms including mutations, rearrangements of the genome, and viral insertions and, under prolonged selection pressures, also has the potential to be an agent of evolutionary change.

The sequences of two frog herpesviruses, Ranid herpesvirus 1 and Ranid herpesvirus 2, were determined. They are respectively 220 859 and 231 801 bp in size and contain 132 and 147 predicted genes. The genomes are related most closely in the central regions, where 40 genes are conserved convincingly. Nineteen of these genes are also conserved in a fish herpesvirus, Ictalurid herpesvirus 1. The terminal regions of the genomes are largely not conserved and contain many of the 15 families of related genes present in each genome. The frog herpesviruses are unique among sequenced herpesviruses in that the three exons of the gene encoding the putative ATPase subunit of terminase are not specified by the same DNA strand and in that they encode a putative DNA (cytosine-5-)-methyltransferase and have extensively methylated genomes.

A splendid tree frog (Pelodryas splendida) presented with subcutaneous edema extending along its dorsum from head to vent, which resolved with improvement of ambient temperature and humidity conditions in its enclosure. Four months later, this same frog presented in a moribund state with intracoelomic fluid accumulation. An intestinal adenocarcinoma, a rarely reported neoplasm in amphibians, was diagnosed post mortem. Neoplasia is one of a number of causes of edema syndrome, which is a nonspecific response to disease and debility in anurans.

The northern leopard frog, Rana pipiens, is vulnerable to a herpesvirus-induced renal tumor. The Lucké renal adenocarcinoma is metastatic as a function of temperature. The cloning procedure of nuclear transplantation has been used to study the differentiation potential of the tumor genome. This paper summarizes current studies of the pathology, virology, and differentiation competence of the Lucké tumor.

The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucké renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well-differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue.

The processes of cell adhesion and active spreading were assessed between frog normal pronephric, pronephric tumor and heterologous liver cells. Confluent monolayers were developed on collagen-coated microcarrier beads, then exposed to homologous or heterologous cells and cultivated with a rotary (orbital) flask culture technique at 23 degrees C. All three cell lines attach and actively spread on the collagen-coated microcarrier beads. Secondary attachment of normal (non-transformed) proliferating cells to their confluent monolayers occurs but cell spreading is restrained. Dissociated pronephric tumor cells adhere and actively spread on the surfaces of normal pronephric cells, and eventually encapsulate them. Normal pronephric cells do not adhere readily to the cell surfaces of pronephric tumor cells grown on microcarrier beads. Tumor cells also attach, actively spread and overgrow heterologous liver cells attached to microcarrier beads. Suboptimal temperatures (17 degrees C) slow tumor cell attachment and spreading on normal cells. Colder temperature (8 degrees C) permits tumor cell attachment and adhesion to normal cell-coated beads but active cell spreading is prohibited. The same temperature retards cell spreading directly on the collagen-coated beads.

Invasion of malignant mouse MO4 cells into embryonic chick heart fragments in confronting organ cultures was arrested for 7 days when the temperature of incubation was lowered to 28 degrees C. Afterwards invasion resumed and progression between days 10 and 17 at 28 degrees C was comparable to that between days 0 and 7 at 37 degrees C. This pattern of progression of MO4 cell invasion at 28 degrees C was unaltered when either MO4 cells or heart fragments or both were preincubated separately at 28 degrees C for 14 days before confrontation with each other. Invasion at 28 degrees C resumed only when MO4 cells and heart tissue had been in immediate contact for at least 7 days. Metabolic labelling with [3H]fucose showed a correlation in time between transient suppression of invasion and transient inhibition of incorporation of fucosylation-precursor molecules into glycoproteins by MO4 cells. The latter activity was far less temperature-sensitive in heart cells. Our observations suggest that metabolic cooperation between invading MO4 cells and heart tissue is essential for progression of invasion in vitro.

The northern leopard frog, Rana pipiens, may be afflicted with a herpesvirus-transmitted renal carcinoma which has the interesting property that its metastatic behavior is temperature-related. PNKT-4B is a cell line derived from a pronephric carcinoma arising in a tadpole. We sought to ascertain if invasion of normal tissue by PNKT-4B cells in three-dimensional confrontation culture in vitro is similarly temperature-dependent. Normal fragments of tadpole and frog organs are invaded by PNKT-4B cells at 28 degrees C but not at 20 degrees C or 21 degrees C. PNKT-4B cells failed to invade tadpole tissues at 7 degrees C. A temperature critical for invasion was sought. Temperatures of 21 degrees C and cooler are invasion-restrictive and 23 degrees C and warmer are invasion-permissive under the conditions of this study. Identification of a critical permissive temperature allows for the characterization of biochemical events which may be activated at the same temperature. The biochemical changes, which are selectively activated and subsequently repressed as tumor cells are cycled through invasion-permissive and invasion-restrictive temperatures, become compelling candidates as reactions involved in, or causal for, malignant invasion.

Fragments of renal carcinoma of the northern leopard frog, Rana pipiens, were cocultured in vitro with small pieces of tadpole heart, frog heart and frog kidney with gyrotory shaking for up to 14 days at 21 degrees C and 28 degrees C. No invasion by renal carcinoma occurred in confrontation cultures at 21 degrees. However, the three normal tissues were invaded by renal carcinoma in confrontation cultures incubated at 28 degrees C. Invasion in vitro by histologically typical renal carcinoma is thus similar to temperature-dependent invasion by the renal carcinoma-derived cell line PNKT-4B and affords an opportunity for the identification of cell or biochemical events which may be activated at invasion-permissive temperature. Cell or biochemical events which are selectively activated and subsequently repressed as the renal tumor is incubated at invasion-permissive and invasion-restrictive temperatures become significant candidates as events involved in, or causal for, malignant invasion.