Next Article in Journal / Special Issue
The Establishment of the Pfizer-Canine Comparative Oncology and Genomics Consortium Biospecimen Repository
Previous Article in Journal
Experimental Animal Models of Arteriovenous Malformation: A Review
Review

Cats, Cancer and Comparative Oncology

University of Tennessee College of Veterinary Medicine, 2407 River Drive, Knoxville, TN 37996, USA
Current Address: University of Minnesota Veterinary Clinical Sciences Department, 1352 Boyd Ave, St Paul, MN 55108, USA.
Academic Editor: Jaime F. Modiano
Vet. Sci. 2015, 2(3), 111-126; https://doi.org/10.3390/vetsci2030111
Received: 25 May 2015 / Revised: 17 June 2015 / Accepted: 24 June 2015 / Published: 30 June 2015
(This article belongs to the Special Issue Comparative Pathogenesis of Cancers in Animals and Humans)

Abstract

Naturally occurring tumors in dogs are well-established models for several human cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous cancers developing in an immunocompetent animal sharing the same environment as humans, shorter lifespan allowing more rapid trial completion and data collection, lack of standard of care for many cancers allowing evaluation of therapies in treatment-naïve populations), but have not been utilized to the same degree in the One Medicine approach to cancer. There are both challenges and opportunities in feline compared to canine models. This review will discuss three specific tumor types where cats may offer insights into human cancers. Feline oral squamous cell carcinoma is common, shares both clinical and molecular features with human head and neck cancer and is an attractive model for evaluating new therapies. Feline mammary tumors are usually malignant and aggressive, with the ‘triple-negative’ phenotype being more common than in humans, offering an enriched population in which to examine potential targets and treatments. Finally, although there is not an exact corollary in humans, feline injection site sarcoma may be a model for inflammation-driven tumorigenesis, offering opportunities for studying variations in individual susceptibility as well as preventative and therapeutic strategies.
Keywords: comparative oncology; feline cancer; animal models comparative oncology; feline cancer; animal models

1. Introduction

‘Cats are not small dogs’ is an oft-quoted phrase in veterinary medicine. Nowhere is this more true than in comparative oncology, and it is both the advantage and disadvantage of the cat as a model.
Although domestic cats have been used as models for various non-neoplastic diseases and are of particular value for investigation of inherited ophthalmic diseases and type 2 diabetes [1,2], to date the dog has been the focus in comparative oncology [3,4]. This may be due, in part, to the fact that the complete feline genome has only very recently become available [5], whereas the canine genome has been available since 2005 [6]. The resources are now available to begin to fully investigate naturally-occurring cancers in cats as models for human diseases beyond the clinical and histological similarities. Greater coverage of the feline genome and development of a feline microarray chip similar to those developed for humans and dogs, allowing genome-wide assessments, would assist in fully investigating cats as cancer models.
Cancer is common in domestic cats, though likely somewhat less common than in dogs [7,8]. Like dogs, cats with cancer have clear benefits over laboratory models of human cancers (i.e., induced tumors or xenografted human cell lines in rodents). Cats and dogs experience the same environmental risk factors as humans and are immunocompetent, more accurately reflecting the complex interplay of genetics and environmental risk factors as well as the role of the immune system and tumor microenvironment. There is greater homology between dogs and humans for key cancer-related genes than there is between rodents and humans [9], and there is also significant homology between cats and humans for specific genes [10,11,12]. Comparative genomics in feline cancers are reviewed in detail elsewhere in this issue [13]. The shorter lifespan and more rapid progression of cancers in animals allows more rapid trial completion and data collection, potentially identifying therapies that are more likely to succeed in human trials. There is a lack of standard of care for many cancers in animals and new therapies are more likely to be evaluated in treatment-naïve patients, which may give better determination of toxicity and efficacy. The cat may be superior to the dog as a model for some specific tumors, e.g., oral squamous cell carcinoma (SCC) and aggressive mammary tumors, due to the increased frequency in this species. Sarcoma formation secondary to inflammation (at injection sites or following trauma), while rarely reported in dogs, is well-recognized in cats, and may offer insights into inflammation-driven tumorigenesis in general. Published feline cell lines for these tumor types are included in Table 1.
When considering potential benefits of the cat as a model, there are some species-specific challenges to be considered. Although 2012 data suggest that there are more cats than dogs owned as pets in the United States, they are less likely to be seen by veterinarians, either at primary care or referral hospitals [14,15,16,17,18]. This effect is more pronounced in cats greater than 9 years of age [17], meaning that cats at highest risk of cancer are least likely to be seen for routine veterinary care. Cat owners are more likely to perceive their pet being stressed by veterinary visits than dog owners [17]. In the specific situation of clinical trials, a recent survey found that most cat owners were unsure about whether they would consider enrolling their cat in a hypothetical trial, though 71% of owners who had previously participated in a clinical trial would consider participating again. Important factors in owners’ decisions included the recommendation of their primary veterinarian, the number of visits, and the risk of discomfort to their cat [19]. Although there are barriers to clinical trials in cats, there are opportunities at every level to improve recruitment including education of the public about the importance of routine veterinary care and the existence of clinical trials, of primary care veterinarians about clinical trial opportunities and of both primary care and specialist veterinarians about ‘feline-friendly’ or low-stress handling techniques.
One of the strengths of the dog in comparative oncology is the relatively genetically homogenous breeds (compared to humans) with breed predispositions to different cancers, simplifying identification of genetic signatures related to cancer predisposition (for example, DNA repair deficiency in Golden Retrievers associated with higher risk of lymphoma) [20]. Dogs have undergone major selection pressure by humans for hundreds, if not thousands, of years, resulting in genetically distinct groups. Most cat breeds developed within the past century and there are fewer genetically distinct breeds than in dogs [21,22]. The fact that there are very few specific breed predispositions reported for cancer in cats may reflect this, although Siamese cats are over-represented in cats with cancer in general, and specifically with mammary gland and intestinal neoplasia [23,24,25]. The recently available feline genome may allow identification of genetic signatures of cancer risk in Siamese compared to other cats.
In terms of using cats as pre-clinical models for assessment of new drugs, thorough consideration needs to be given to drug metabolism and pharmacokinetics in this species before determination of applicability in people can be made. Cats are known to have reduced overall hepatic glucuronidation capacity compared to dogs and humans, though this seems to be drug-specific [26,27]. Consideration of metabolic pathways prior to clinical trials of potential new drugs in cats is recommended. Examples of chemotherapeutic drugs with differing toxicities in dogs and cats include cisplatin (fatal pulmonary edema in cats) [28], 5-fluorouracil (fatal neurotoxicity in cats, which is not due to reduced DPD function) [29], CCNU (lower apparent risk of hepatotoxicity in cats) [30], doxorubicin (nephrotoxic in cats, cardiotoxic in dogs) [31] and ifosfamide (higher maximum tolerated dose in cats) [31].
Despite the potential challenges, investigating cancer in cats is likely to add to the field of comparative oncology and complement the use of the canine model, especially in some specific instances.

2. Feline Oral Squamous Cell Carcinoma

Squamous cell carcinoma represents 70–80% of all oral tumors in domestic cats. Increased risk has been associated with exposure to environmental tobacco smoke, flea collars and feeding canned food [32], although specific risk factors are not identified in most patients. Tobacco use, along with alcohol, is a major risk factor in human head and neck cancer (HHNC), most of which are SCC affecting the oral/oropharyngeal cavity [33,34]. Papillomavirus infection plays a role in a significant proportion of HHNC, and is associated with less aggressive disease and better outcome [34]. Although papillomavirus may play a role in feline cutaneous SCC and has been isolated from oral papillomas in cats, it has not been demonstrated to be involved in the vast majority of feline oral SCC [35,36,37,38]. In humans, it seems that many oral/oropharyngeal SCC arise from pre-existing disorders such as leukoplakia and erythroplakia [34]. Such progression has not been identified in feline oral SCC, although inflammatory conditions like periodontal disease and stomatitis are common [39]. It is possible that there are similar pre-malignant lesions in cats which, if identified, may be models for chemoprevention or other intervention strategies. In both humans and cats, head and neck SCC is locally invasive, often diagnosed late, and is challenging to treat [33,34,40]. In cats, local disease is typically life-limiting and metastasis is less commonly reported than in humans, though may be underestimated since survival times are short because of advanced stage at diagnosis and poor response to local therapies [33,40]. The most common laboratory models for HHNC are induced tumors in the oral cavity of hamsters or rats, which have shed light on tumor initiation by carcinogens such as tobacco or betel nut, and subcutaneous xenograft models [41]. Feline oral SCC more closely mimics the natural behavior of HHNC and likely more accurately predicts response to treatment than induced tumors in laboratory animals.
As well as clinical features, feline oral SCC shares many molecular features with HHNC, including high frequency of epidermal growth factor (EGFR) over-expression (although not proven to be prognostic in cats) [34,42,43,44,45,46], altered p53 expression [34,47,48], dysregulated CK2 expression [49,50], markers of angiogenesis [34,46,51,52] and cyclooxygenase and lipoxygenase enzyme overexpression [34,53,54,55,56].
Feline oral SCC (either in clinical patients, cell lines or immunohistochemical studies) has been used as a model for tumor hypoxia (which may be targeted to improve responses to chemo- or radio-therapy) [57] and mechanisms and treatment of bone invasion [51,58,59,60,61]. EGFR is a druggable target in HHNC [42], and the feline and human EGFR sequences are highly homologous [10]. The EGFR small molecule inhibitor gefitinib is approved for use in HHNC, but has only a modest effect as monotherapy and, even in patients that initially respond, resistance commonly develops after long-term treatment [62]. Gefitinib resistance has been evaluated in a feline SCC cell line [10,63] and the cat could be a useful model for studying mechanisms of, and strategies to circumvent, EGFR-inhibitor resistance (e.g., RNA interference) [10]. Increased polyamine content is a feature of many tumors in humans, including HNC, and targeting polyamine synthesis with ornithine decarboxylase (ODC) inhibitors has been proposed as a possible therapeutic strategy [64]. A combination of alpha difluoromethylornithine (DFMO), an ODC inhibitor, with a novel membrane transport inhibitor to increase intracellular DFMO concentrations showed positive results in a murine model, with a 71% complete response rate [65]. In feline patients with naturally occurring oral SCC there was some indication of activity, but results were more modest (16.7% partial response rate, 50% stable disease). This may offer more realistic expectation of what might be expected from this type of therapy in people [66]. Inhibition of CK2 is effective in rodent xenograft models of human prostate and head and neck cancers [67,68,69] and small molecule CK2 inhibitors are in early clinical trials. In vitro results in feline SCC show similar results to human cell lines [50], and a clinical trial of RNA interference targeting CK2 is underway in cats with oral SCC, which may inform future human studies.
Overall, current standard treatments for feline oral SCC (surgery, radiation and chemotherapy) have almost universally poor outcomes, with median survival times in the order of a few months [40,70,71]. Better results are seen in small tumors [71], but as most patients have advanced disease at the time of diagnosis, treatment is typically palliative. With the grave prognosis and lack of effective standard of care, it is reasonable to offer experimental therapies to cats and owners at the time of diagnosis, and therapies can be assessed in a treatment-naïve population who may be more likely to respond. Potential avenues for comparative investigations in feline SCC include new EGFR inhibitors, including in the setting of gefitinib-resistance, CK2 inhibition alone and in combination with chemo- or radio-therapy, novel COX/LOX inhibitors, methods to reverse hypoxia in combination with other therapies, and anti-angiogenic therapies. Toceranib phosphate (Palladia, Zoetis) is a multi-kinase inhibitor which has shown some anecdotal efficacy in feline oral SCC. It does not inhibit EGFR, so the mechanism of its activity is currently unknown, and an investigation currently underway evaluating expression of toceranib targets in feline oral SCC [72] may identify new targets in HHNC as well.

3. Feline Mammary Gland Tumors

In cats, unlike dogs, the vast majority of mammary gland tumors are malignant, and multiple tumors and metastasis are common at diagnosis [73,74,75,76]. Thus, cats with mammary cancer may offer a larger population of aggressive malignancies to study. The epidemiology of mammary gland tumors in cats and people is similar, with age [23,74] and hormone exposure [73,77] being major risk factors. There is a breed predisposition in Siamese cats, which are more likely to develop mammary tumors and at a younger age than other cat breeds [23,73]. Now that the feline genome is available, Siamese cats may be a model for genetic risk of breast cancer and other neoplasia, given their increased risk of several tumor types. Germline mutations in BRCA1 and BRCA2 genes are associated with familial breast cancer risk in women, although the majority of breast cancers are sporadic in nature [78]. BRCA mutations have not been found in cats with mammary cancer [79]. Since there is a breed predisposition (if not a proven inherited risk), studying Siamese cats specifically may be more likely to identify these or other genetic abnormalities predisposing to mammary cancer.
In contrast to breast cancer in women, feline mammary tumors are more likely to be hormone (estrogen and progesterone) receptor negative, though differing methodologies and scoring makes comparisons between studies challenging [80,81,82,83,84]. Epidermal growth factor receptor 2 (HER2, neu, erbb2) is commonly over-expressed in human breast cancer and is a druggable target, with trastuzumab (Herceptin®, Genentech) improving outcome in women with HER2-expressing breast cancer [85]. Increased HER2 expression and activity, demonstrated by increased downstream AKT activation, is also seen in feline mammary carcinomas, though there is variation among studies with regard to the rate of HER2 expression and methodologies used [79,84,86,87,88,89,90]. Recent studies have used the human standard methodology (HercepTestTM, Dako) for evaluation of HER2 in feline mammary tumors [87,90,91] which may offer a useful standard for future studies. Concurrent evaluation of HER2 mRNA expression (as well as protein expression) may add to the understanding of its role in feline mammary gland tumors, though currently published studies are discrepant in terms of relative HER2 expression between normal and neoplastic tissues [11,84,91]. There appears to be a significant proportion of feline mammary carcinomas which are ‘triple-negative’ i.e., hormone receptor negative and not over-expressing HER2 [79,84]. This phenotype is generally associated with a poorer prognosis in humans and is challenging to treat because of a lack of specific targets. Additional molecular analyses distinguish several other subtypes of breast cancer, e.g., luminal A, luminal B and claudin low, and similar subtypes may exist in cats [84,92]. The overall increased likelihood of aggressive mammary cancer in cats compared to humans offers opportunities to study factors such as drivers of metastasis and potential treatments for triple-negative tumors. Cats may also be a useful model for evaluating new HER2-targeted therapies. A recent study vaccinated healthy cats with HER2 DNA and induced specific T cell responses to self-HER2 in four out of 10 cats [93]. Cats with naturally occurring mammary cancer could be used for rapid pre-clinical assessment of efficacy of HER2 vaccination as well as to assess determinants of response, given the variability in induced immunity. When considering cats as a model for HER2-targeted therapies however, strong consideration needs to be given to the methodologies used to assess HER2 protein expression due to variability between studies, as well as the recently identified sequence variants in HER2 which may impact its affinity for targeted therapies such as trastuzumab, as is seen in humans [91].

4. Injection Site Sarcoma

Inflammation is well-established as a risk factor for several cancers in people and similar risk factors likely exist in dogs and cats [94,95]. Although there are sporadic cases of sarcomas associated with various implants and injections in humans and animals [96,97,98,99,100], cats appear to have a unique propensity for sarcomagenesis associated with trauma and/or inflammation. Injection site sarcoma (ISS) is a well-recognized phenomenon in cats, especially in association with vaccine administration. Estimates in the US and UK range from one case of ISS per 1,000–12,500 cats vaccinated [101,102]. Most ISS in cats are fibrosarcomas, and common histologic features include multinucleate giant cells, myofibroblastic differentiation and inflammatory infiltrate (lymphocytes and macrophages), which are not typically seen in feline non-injection site fibrosarcomas [103,104,105,106]. Intra-ocular sarcoma formation following trauma or other ocular disease is also recognized in cats [107]. No risk factors have been identified to determine why some cats develop sarcomas following trauma or injection. It is hypothesized that in these cats the immune response to injection or trauma is inappropriate and excessive, resulting in chronic inflammation causing proliferation and malignant transformation of fibroblasts. Chronic inflammation increases the risk for many carcinomas in people, though the only clear association between sarcomagenesis and chronic inflammation is in the case of Kaposi’s sarcoma (KS). KS is frequently associated with inflammatory infiltrate and Kaposi sarcoma-associated herpesvirus (KSHV) proteins activate factors including Th2 lymphocytes, cyclooxygenase 2 and NFκB resulting in a pro-tumor inflammatory microenvironment [108]. ISS in cats may model inflammation-associated tumorigenesis in general, which likely has common pathways in many different tumor histologies. As not every cat vaccinated develops ISS, not every person with chronic inflammatory disease develops associated cancer. Given that lifestyle factors such as environment and diet are likely more controllable in cats than in people, genomic screening in cats that develop ISS may identify features of the immune system or other factors related to tumor development. Such features may also be present in humans, and could identify individuals who may benefit from early intervention or more frequent monitoring. As well as a model for identifying risk factors, ISS may be a model for prevention or therapy. A recent development in ISS treatment is the approval of feline interleukin-2 recombinant canarypox virus (Oncept Il-2) to reduce local recurrence following standard-of-care therapy [109], indicating that manipulation of the immune system in this, and other inflammation-driven tumors, may be of therapeutic benefit. Further elucidation of the nature of feline ISS-associated inflammation (e.g., assessing cytokine profiles, T cell subtypes, and tumor-infiltrating macrophages) may be a first step in identifying strategies to reduce tumor-promoting inflammation and/or promote anti-tumor inflammation. Potential chemoprevention strategies could likely be evaluated in a relatively timely fashion since it appears that most ISS develop within 3 years of vaccination, though latent periods of up to 10 years are reported [110,111].

5. Conclusions

Although a decade behind their canine counterparts, cats have great potential to contribute to comparative oncology. Areas of especial focus may include head and neck squamous cell carcinoma, aggressive mammary tumors and inflammation-associated tumorigenesis. Areas for progress in order to exploit the full potential of the feline model include standardization of target assessments, development of efficient genome-wide analyses (e.g., feline-specific microarrays) and education of the public and veterinary communities about clinical trials and other comparative opportunities.
Table 1. Feline squamous cell carcinoma, mammary gland carcinoma and injection-site sarcoma cell lines used in published research.
Table 1. Feline squamous cell carcinoma, mammary gland carcinoma and injection-site sarcoma cell lines used in published research.
Tumor TypeCell Line
Head and neck squamous cell carcinomaSCCF1 [112]
SCCF1-Luc (luciferase-expressing) [47]
SCCF1G (gefitinib-resistant) [10]
SCCF2 [58]
SCCF2-Luc
SCCF3 [58]
SCCF3-Luc
Mammary gland tumorK12 [113]
JM [114]
FYMp (primary) [115]
FKNp [115]
FNNm (metastatic) [115]
FONp [116]
FONm [116]
FMCp1 [115]
FMCp2 [115]
FMCm [115]
FRM [117]
NAC [118]
K248C [119]
K248P [119]
DT09/06 [120]
Injection site sarcomaFSA [121]
FSB [121]
FS1 [122]
FS2 [122]
FS3 [122]
FS4 [122]
VAS-1 [123]
VAS-2 [123]
VAS-3 [123]
VAS-4 [123]
VAS-5 [123]
JB [124]
JBLM [124]

Conflicts of Interest

The author declares no conflict of interest.

References and Notes

  1. Henson, M.S.; O’Brien, T.D. Feline models of type 2 diabetes mellitus. ILAR J. 2006, 47, 234–242. [Google Scholar] [CrossRef] [PubMed]
  2. Narfstrom, K.; Deckman, K.H.; Menotti-Raymond, M. Cats: A gold mine for ophthalmology. Ann. Rev. Anim. Biosci. 2013, 1, 157–177. [Google Scholar] [CrossRef] [PubMed]
  3. Gordon, I.; Paoloni, M.; Mazcko, C.; Khanna, C. The Comparative Oncology Trials Consortium: Using spontaneously occurring cancers in dogs to inform the cancer drug development pathway. PLoS Med. 2009, 6, e1000161. [Google Scholar] [CrossRef] [PubMed]
  4. Gordon, I.K.; Khanna, C. Modeling opportunities in comparative oncology for drug development. ILAR J. 2010, 51, 214–220. [Google Scholar] [CrossRef] [PubMed]
  5. Tamazian, G.; Simonov, S.; Dobrynin, P.; Makunin, A.; Logachev, A.; Komissarov, A.; Schevchenko, A.; Brukhin, V.; Cherkasov, N.; Svitin, A.; et al. Annotated features of domestic cat —Felis catus genome. GigaScience. 2014, 3. Available online: http://www.gigasciencejournal.com/content/3/1/13 (accessed on 25 June 2015). [CrossRef] [PubMed][Green Version]
  6. Lindblad-Toh, K.; Wade, C.M.; Mikkelsen, T.S.; Karlsson, E.K.; Jaffe, D.B.; Kamal, M.; Clamp, M.; Chang, J.L.; Kulbokas, E.J., 3rd; Zody, M.C.; et al. Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 2005, 438, 803–819. [Google Scholar] [CrossRef] [PubMed]
  7. Butler, L.M.; Bonnett, B.N.; Page, R.L. Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed.; Withrow, S.J., Vail, D.M., Page, R.L., Eds.; Elsevier Saunders: St Louis, MO, USA, 2012; pp. 68–82. [Google Scholar]
  8. MacVean, D.W.; Monlux, A.W.; Anderson, P.S., Jr.; Silberg, S.L.; Roszel, J.F. Frequency of canine and feline tumors in a defined population. Vet. Pathol. 1978, 15, 700–715. [Google Scholar] [CrossRef] [PubMed]
  9. Paoloni, M.; Khanna, C. Translation of new cancer treatments from pet dogs to humans. Nat. Rev. Cancer 2008, 8, 147–156. [Google Scholar] [CrossRef] [PubMed]
  10. Bergkvist, G.T.; Argyle, D.J.; Pang, L.Y.; Muirhead, R.; Yool, D.A. Studies on the inhibition of feline EGFR in squamous cell carcinoma: Enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors. Cancer Biol. Therapy 2011, 11, 927–937. [Google Scholar] [CrossRef]
  11. De Maria, R.; Olivero, M.; Iussich, S.; Nakaichi, M.; Murata, T.; Biolatti, B.; Di Renzo, M.F. Spontaneous feline mammary carcinoma is a model of HER2 overexpressing poor prognosis human breast cancer. Cancer Res. 2005, 65, 907–912. [Google Scholar] [PubMed]
  12. Santos, S.; Bastos, E.; Baptista, C.S.; Sá, D.; Caloustian, C.; Guedes-Pinto, H.; Gärtner, F.; Gut, I.G.; Chaves, R. Sequence variants and haplotype analysis of cat ERBB2 gene: A survey on spontaneous cat mammary neoplastic and non-neoplastic lesions. Int. J. Mol. Sci. 2012, 13, 2783–2800. [Google Scholar] [CrossRef] [PubMed]
  13. Thomas, R. Cytogenomics of Feline Cancers: Advances and Opportunities. Vet. Sci. 2015. in preparation. [Google Scholar]
  14. Bartlett, P.C.; Van Buren, J.W.; Neterer, M.; Zhou, C. Disease surveillance and referral bias in the veterinary medical database. Prev. Vet. Med. 2010, 94, 264–271. [Google Scholar] [CrossRef] [PubMed]
  15. Teclaw, R.; Mendlein, J.; Garbe, P.; Mariolis, P. Characteristics of pet populations and households in the Purdue Comparative Oncology Program catchment area, 1988. J. Amer. Vet. Med. Assoc. 1992, 201, 1725–1729. [Google Scholar]
  16. Volk, J.O.; Felsted, K.E.; Thomas, J.G.; Siren, C.W. Executive summary of phase 2 of the Bayer veterinary care usage study. J. Amer. Vet. Med. Assoc. 2011, 239, 1311–1316. [Google Scholar] [CrossRef] [PubMed]
  17. Volk, J.O.; Felsted, K.E.; Thomas, J.G.; Siren, C.W. Executive summary of the Bayer veterinary care usage study. J. Amer. Vet. Med. Assoc. 2011, 238, 1275–1282. [Google Scholar] [CrossRef] [PubMed]
  18. American Veterinary Medical Association. U.S. Pet Ownership Statistics. 2012. Available online: https://www.avma.org/KB/Resources/Statistics/Pages/Market-research-statistics-US-pet-ownership.aspx (accessed on 19 March 2015).
  19. Gruen, M.E.; Jiamachello, K.N.; Thomson, A.; Lascelles, B.D. Clinical trials involving cats: What factors affect owner participation? J. Feline Med. Surg. 2014, 16, 727–735. [Google Scholar] [CrossRef] [PubMed]
  20. Thamm, D.H.; Grunerud, K.K.; Rose, B.J.; Vail, D.M.; Bailey, S.M. DNA repair deficiency as a susceptibility marker for spontaneous lymphoma in golden retriever dogs: A case-control study. PLoS ONE 2013, 8, e69192. [Google Scholar] [CrossRef] [PubMed]
  21. Lipinski, M.J.; Froenicke, L.; Baysac, K.C.; Billings, N.C.; Leutenegger, C.M.; Levy, A.M.; Longeri, M.; Niini, T.; Ozpinar, H.; Slater, M.R.; et al. The ascent of cat breeds: Genetic evaluations of breeds and worldwide random-bred populations. Genomics 2008, 91, 12–21. [Google Scholar] [CrossRef] [PubMed]
  22. Kurushima, J.D.; Lipinski, M.J.; Gandolfi, B.; Froenicke, L.; Grahn, J.C.; Grahn, R.A.; Lyons, L.A. Variation of cats under domestication: Genetic assignment of domestic cats to breeds and worldwide random-bred populations. Anim. Genet. 2013, 44, 311–324. [Google Scholar] [CrossRef] [PubMed]
  23. Egenvall, A.; Bonnett, B.N.; Haggstrom, J.; Ström Holst, B.; Möller, L.; Nødtvedt, A. Morbidity of insured Swedish cats during 1999–2006 by age, breed, sex, and diagnosis. J. Feline Med. Surg. 2010, 12, 948–959. [Google Scholar] [CrossRef] [PubMed]
  24. Egenvall, A.; Nødtvedt, A.; Haggstrom, J.; Ström Holst, B.; Möller, L.; Bonnett, B.N. Mortality of life-insured Swedish cats during 1999–2006: Age, breed, sex, and diagnosis. J. Vet. Intern. Med. 2009, 23, 1175–1183. [Google Scholar] [CrossRef] [PubMed]
  25. Rissetto, K.; Villamil, J.A.; Selting, K.A.; Tyler, J.; Henry, C.J. Recent trends in feline intestinal neoplasia: An epidemiologic study of 1,129 cases in the veterinary medical database from 1964 to 2004. J. Am. Anim. Hosp. Assoc. 2011, 47, 28–36. [Google Scholar] [CrossRef] [PubMed]
  26. Ebner, T.; Schänzle, G.; Weber, W.; Sent, U.; Elliott, J. In vitro glucuronidation of the angiotensin II receptor antagonist telmisartan in the cat: A comparison with other species. J. Vet. Pharmacol. Therapeut. 2013, 36, 154–160. [Google Scholar] [CrossRef] [PubMed]
  27. van Beusekom, C.D.; Fink-Gremmels, J.; Schrickx, J.A. Comparing the glucuronidation capacity of the feline liver with substrate-specific glucuronidation in dogs. J. Vet. Pharmacol. Therapeut. 2014, 37, 18–24. [Google Scholar] [CrossRef] [PubMed]
  28. Knapp, D.W.; Richardson, R.C.; DeNicola, D.B.; Long, G.G.; Blevins, W.E. Cisplatin toxicity in cats. J. Vet. Intern. Med. 1987, 1, 29–35. [Google Scholar] [CrossRef] [PubMed]
  29. Saba, C.F.; Schmiedt, C.W.; Freeman, K.G.; Edwards, G.L. Indirect assessment of dihydropyrimidine dehydrogenase activity in cats. Vet. Compar. Oncol. 2013, 11, 265–271. [Google Scholar] [CrossRef] [PubMed]
  30. Musser, M.L.; Quinn, H.T.; Chretin, J.D. Low apparent risk of CCNU (lomustine)-associated clinical hepatotoxicity in cats. J. Feline Med. Surg. 2012, 14, 871–875. [Google Scholar] [CrossRef] [PubMed]
  31. Gustafson, D.L.; Page, R.L. Cancer Chemotherapy. In Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed.; Withrow, S.J., Vail, D.M., Page, R.L., Eds.; Elsevier Saunders: St Louis, MO, USA, 2012; pp. 157–179. [Google Scholar]
  32. Bertone, E.R.; Snyder, L.A.; Moore, A.S. Environmental and lifestyle risk factors for oral squamous cell carcinoma in domestic cats. J. Vet. Intern. Med. 2003, 17, 557–562. [Google Scholar] [CrossRef] [PubMed]
  33. Belcher, R.; Hayes, K.; Fedewa, S.; Chen, A.Y. Current treatment of head and neck squamous cell cancer. J. Surg. Oncol. 2014, 110, 551–574. [Google Scholar] [CrossRef] [PubMed]
  34. Huber, M.A.; Tantiwongkosi, B. Oral and oropharyngeal cancer. Med. Clin. North Amer. 2014, 98, 1299–1321. [Google Scholar] [CrossRef] [PubMed]
  35. Munday, J.S.; Aberdein, D. Loss of retinoblastoma protein, but not p53, is associated with the presence of papillomaviral DNA in feline viral plaques, Bowenoid in situ carcinomas, and squamous cell carcinomas. Vet. Pathol. 2012, 49, 538–545. [Google Scholar] [CrossRef] [PubMed]
  36. Munday, J.S.; Fairley, R.A.; Mills, H.; Kiupel, M.; Vaatstra, B.L. Oral Papillomas Associated With Felis catus Papillomavirus Type 1 in 2 Domestic Cats. Vet. Pathol. 2015. Available online: http://vet.sagepub.com/content/early/2015/01/02/0300985814565133 (accessed on 26 June 2015). [CrossRef] [PubMed]
  37. Munday, J.S.; Howe, L.; French, A.; Squires, R.A.; Sugiarto, H. Detection of papillomaviral DNA sequences in a feline oral squamous cell carcinoma. Res. Vet. Sci. 2009, 86, 359–361. [Google Scholar] [CrossRef] [PubMed]
  38. Munday, J.S.; French, A.F. Felis catus papillomavirus types 1 and 4 are rarely present in neoplastic and inflammatory oral lesions of cats. Res. Vet. Sci. 2015. Available online: http://www.sciencedirect.com/science/article/pii/S0034528815000569. [CrossRef] [PubMed]
  39. Farcas, N.; Lommer, M.J.; Kass, P.H.; Verstraete, F.J. Dental radiographic findings in cats with chronic gingivostomatitis (2002–2012). J. Amer. Vet. Med. Assoc. 2014, 244, 339–345. [Google Scholar] [CrossRef] [PubMed]
  40. Liptak, J.M.; Withrow, S.J. Cancer of the Gastrointestinal Tract. In Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed.; Withrow, S.J., Vail, D.M., Page, R.L., Eds.; Elsevier Saunders: St Louis, MO, USA, 2012; pp. 381–431. [Google Scholar]
  41. Mognetti, B.; Di Carlo, F.; Berta, G.N. Animal models in oral cancer research. Oral Oncol. 2006, 42, 448–460. [Google Scholar] [CrossRef] [PubMed]
  42. Ribeiro, F.A.; Noguti, J.; Oshima, C.T.; Ribeiro, D.A. Effective targeting of the epidermal growth factor receptor (EGFR) for treating oral cancer: A promising approach. Anticancer Res. 2014, 34, 1547–1552. [Google Scholar] [PubMed]
  43. Bergkvist, G.T.; Argyle, D.J.; Morrison, L.; MacIntyre, N.; Hayes, A.; Yool, D.A. Expression of epidermal growth factor receptor (EGFR) and Ki67 in feline oral squamous cell carcinomas (FOSCC). Vet. Compar. Oncol. 2011, 9, 106–117. [Google Scholar] [CrossRef] [PubMed]
  44. Looper, J.S.; Malarkey, D.E.; Ruslander, D.; Proulx, D.; Thrall, D.E. Epidermal growth factor receptor expression in feline oral squamous cell carcinomas. Vet. Compar. Oncol. 2006, 4, 33–40. [Google Scholar] [CrossRef] [PubMed]
  45. Sabattini, S.; Marconato, L.; Zoff, A.; Morini, M.; Scarpa, F.; Capitani, O.; Bettini, G. Epidermal growth factor receptor expression is predictive of poor prognosis in feline cutaneous squamous cell carcinoma. J. Feline Med. Surg. 2010, 12, 760–768. [Google Scholar] [CrossRef] [PubMed]
  46. Yoshikawa, H.; Ehrhart, E.J.; Charles, J.B.; Thamm, D.H.; Larue, S.M. Immunohistochemical characterization of feline oral squamous cell carcinoma. Amer. J. Vet. Res. 2012, 73, 1801–1806. [Google Scholar] [CrossRef] [PubMed]
  47. Tannehill-Gregg, S.H.; Levine, A.L.; Rosol, T.J. Feline head and neck squamous cell carcinoma: A natural model for the human disease and development of a mouse model. Vet. Compar. Oncol. 2006, 4, 84–97. [Google Scholar] [CrossRef] [PubMed]
  48. Snyder, L.A.; Bertone, E.R.; Jakowski, R.M.; Booner, M.S.; Jennings-Ritchie, J.; Moore, A.S. p53 expression and environmental tobacco smoke exposure in feline oral squamous cell carcinoma. Vet. Pathol. 2004, 41, 209–214. [Google Scholar] [CrossRef] [PubMed]
  49. Faust, R.A.; Gapany, M.; Tristani, P.; Davis, A.; Adams, G.L.; Ahmed, K. Elevated protein kinase CK2 activity in chromatin of head and neck tumors: Association with malignant transformation. Cancer Lett. 1996, 101, 31–35. [Google Scholar] [CrossRef]
  50. Cannon, C.M.; Trembley, J.H.; Modiano, J.F.; Cespedes Gomez, O.; Kren, B.; Unger, G.; Ahmed, K. CK2 inhibition in feline cancer cell lines using synthetic oligonucleotides. In Proceedings of the American Veterinary Internal Medicine Forum, Seattle, WA, USA, June 2013.
  51. Wypij, J.M.; Fan, T.M.; Fredrickson, R.L.; Barger, A.M.; de Lorimier, L.P.; Charney, S.C. In vivo and in vitro efficacy of zoledronate for treating oral squamous cell carcinoma in cats. J. Vet. Intern. Med. 2008, 22, 158–163. [Google Scholar] [CrossRef] [PubMed]
  52. Moriyama, M.; Kumagai, S.; Kawashiri, S.; Kojima, K.; Kakihara, K.; Yamamoto, E. Immunohistochemical study of tumour angiogenesis in oral squamous cell carcinoma. Oral Oncol. 1997, 33, 369–374. [Google Scholar] [CrossRef]
  53. Hayes, A.; Scase, T.; Miller, J.; Murphy, S.; Sparkes, A.; Adams, V. COX-1 and COX-2 expression in feline oral squamous cell carcinoma. J. Compar. Pathol. 2006, 135, 93–99. [Google Scholar] [CrossRef] [PubMed]
  54. Wakshlag, J.J.; Peters-Kennedy, J.; Bushey, J.J.; Loftus, J.P. 5-lipoxygenase expression and tepoxalin-induced cell death in squamous cell carcinomas in cats. Amer. J. Vet. Res. 2011, 72, 1369–1377. [Google Scholar] [CrossRef] [PubMed]
  55. Wang, Z.M.; Liu, J.; Liu, H.B.; Ye, M.; Zhang, Y.F.; Yang, D.S. Abnormal COX2 protein expression may be correlated with poor prognosis in oral cancer: A meta-analysis. BioMed Res. Int. 2014. Available online: http://www.hindawi.com/journals/bmri/2014/364207/ (accessed on 25 June 2015). [CrossRef] [PubMed]
  56. Celenk, F.; Bayramoglu, I.; Yilmaz, A.; Menevse, A.; Bayazit, Y. Expression of cyclooxygenase-2, 12-lipoxygenase, and inducible nitric oxide synthase in head and neck squamous cell carcinoma. J. Craniofac. Surg. 2013, 24, 1114–1117. [Google Scholar] [CrossRef] [PubMed]
  57. Ballegeer, E.A.; Madrill, N.J.; Berger, K.L.; Agnew, D.W.; McNiel, E.A. Evaluation of hypoxia in a feline model of head and neck cancer using 64Cu-ATSM positron emission tomography/computed tomography. BMC Cancer. 2013, 13. Available online: http://www.biomedcentral.com/1471–2407/13/218 (accessed on 25 June 2015). [CrossRef] [PubMed]
  58. Martin, C.K.; Dirksen, W.P.; Shu, S.T.; Werbeck, J.L.; Thudi, N.K.; Yamaguchi, M.; Wolfe, T.D.; Heller, K.N.; Rosol, T.J. Characterization of bone resorption in novel in vitro and in vivo models of oral squamous cell carcinoma. Oral Oncol. 2012, 48, 491–499. [Google Scholar] [CrossRef] [PubMed]
  59. Martin, C.K.; Tannehill-Gregg, S.H.; Wolfe, T.D.; Rosol, T.J. Bone-invasive oral squamous cell carcinoma in cats: Pathology and expression of parathyroid hormone-related protein. Vet. Pathol. 2011, 48, 302–312. [Google Scholar] [CrossRef] [PubMed]
  60. Martin, C.K.; Dirksen, W.P.; Carlton, M.M.; Lanigan, L.G.; Pillai, S.P.; Werbeck, J.L.; Simmons, J.K.; Hildreth, B.E., 3rd; London, C.A.; Toribio, R.E.; Rosol, T.J. Combined zoledronic acid and meloxicam reduced bone loss and tumour growth in an orthotopic mouse model of bone-invasive oral squamous cell carcinoma. Vet. Compar. Oncol. 2013. Available online: http://onlinelibrary.wiley.com/doi/10.1111/vco.12037/epdf (accessed on 25 June 2015). [CrossRef]
  61. Martin, C.K.; Werbeck, J.L.; Thudi, N.K.; Lanigan, L.G.; Wolfe, T.D.; Toribio, R.E.; Rosol, T.J. Zoledronic acid reduces bone loss and tumor growth in an orthotopic xenograft model of osteolytic oral squamous cell carcinoma. Cancer Res. 2010, 70, 8607–8616. [Google Scholar] [CrossRef] [PubMed]
  62. Chen, L.F.; Cohen, E.E.; Grandis, J.R. New strategies in head and neck cancer: Understanding resistance to epidermal growth factor receptor inhibitors. Clin. Cancer Res. 2010, 16, 2489–2495. [Google Scholar] [CrossRef] [PubMed]
  63. Pang, L.Y.; Bergkvist, G.T.; Cervantes-Arias, A.; Yool, D.A.; Muirhead, R.; Argyle, D.J. Identification of tumour initiating cells in feline head and neck squamous cell carcinoma and evidence for gefitinib induced epithelial to mesenchymal transition. Vet. J. 2012, 193, 46–52. [Google Scholar] [CrossRef] [PubMed]
  64. Battaglia, V.; DeStefano Shields, C.; Murray-Stewart, T.; Casero , R.A., Jr. Polyamine catabolism in carcinogenesis: Potential targets for chemotherapy and chemoprevention. Amino Acids 2014, 46, 511–519. [Google Scholar] [CrossRef] [PubMed]
  65. Chen, Y.; Weeks, R.S.; Burns, M.R.; Boorman, D.W.; Klein-Szanto, A.; O’Brien, T.G. Combination therapy with 2-difluoromethylornithine and a polyamine transport inhibitor against murine squamous cell carcinoma. Int. J. Cancer 2006, 118, 2344–2349. [Google Scholar] [CrossRef] [PubMed]
  66. Skorupski, K.A.; O’Brien, T.G.; Guerrero, T.; Rodrigeuz, C.O.; Burns, M.R. Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma. Vet. Compar. Oncol. 2011, 9, 275–282. [Google Scholar] [CrossRef] [PubMed]
  67. Trembley, J.H.; Unger, G.M.; Korman, V.L.; Tobolt, D.K.; Kazimierczuk, Z.; Pinna, L.A.; Kren, B.T.; Ahmed, K. Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells. Cancer Lett. 2012, 315, 48–58. [Google Scholar] [CrossRef] [PubMed]
  68. Unger, G.M.; Kren, B.T.; Korman, V.L.; Kimbrough, T.G.; Vogel, R.I.; Ondrey, F.G.; Trembley, J.H.; Ahmed, K. Mechanism and efficacy of sub-50-nm tenfibgen nanocapsules for cancer cell-directed delivery of anti-CK2 RNAi to primary and metastatic squamous cell carcinoma. Mol. Cancer Ther. 2014, 13, 2018–2029. [Google Scholar] [CrossRef] [PubMed]
  69. Pierre, F.; Chua, P.C.; O’Brien, S.E.; Siddiqui-Jain, A.; Bourbon, P.; Haddach, M.; Michaux, J.; Nagasawa, J.; Schwaebe, M.K.; Stefan, E.; et al. Pre-clinical characterization of CX-4945, a potent and selective small molecule inhibitor of CK2 for the treatment of cancer. Mol. Cell. Biochem. 2011, 356, 37–43. [Google Scholar] [CrossRef] [PubMed]
  70. Marconato, L.; Buchholz, J.; Keller, M.; Bettini, G.; Valenti, P.; Kaser-Hotz, B. Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: A pilot study. Vet. Compar. Oncol. 2013, 11, 101–112. [Google Scholar] [CrossRef] [PubMed]
  71. Poirier, V.J.; Kaser-Hotz, B.; Vail, D.M.; Straw, R.C. Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma. Vet. Radiol. Ultrasound 2013, 54, 81–88. [Google Scholar] [PubMed]
  72. VetCancerTrials.org. Available online: http://www.vetcancertrials.org/studies/analysis-of-vegfr-pdgfr-and-c-kit-in-feline-oral-squamous-cell-carcinoma (accessed on 12 May 2015).
  73. Hayes, H.M., Jr.; Milne, K.L.; Mandell, C.P. Epidemiological features of feline mammary carcinoma. Vet. Rec. 1981, 108, 476–479. [Google Scholar] [CrossRef] [PubMed]
  74. Sorenmo, K.U.; Worley, D.R.; Goldschmidt, M.H. Tumors of the Mammary Gland. In Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed.; Withrow, S.J., Vail, D.M., Page, R.L., Eds.; Elsevier Saunders: St Louis, MO, USA, 2012; pp. 538–556. [Google Scholar]
  75. Benjamin, S.A.; Lee, A.C.; Saunders, W.J. Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles. Vet. Pathol. 1999, 36, 423–436. [Google Scholar] [CrossRef] [PubMed]
  76. Sorenmo, K.U.; Kristiansen, V.M.; Cofone, M.A.; Shofer, F.S.; Breen, A.M.; Langeland, M.; Mongil, C.M.; Grondahl, A.M.; Teige, J.; Goldschmidt, M.H. Canine mammary gland tumours; A histological continuum from benign to malignant; Clinical and histopathological evidence. Vet. Compar. Oncol. 2009, 7, 162–172. [Google Scholar] [CrossRef] [PubMed]
  77. Overley, B.; Shofer, F.S.; Goldschmidt, M.H.; Sherer, D.; Sorenmo, K.U. Association between ovarihysterectomy and feline mammary carcinoma. J. Vet. Intern. Med. 2005, 19, 560–563. [Google Scholar] [CrossRef] [PubMed]
  78. Taylor, M.R. Genetic testing for inherited breast and ovarian cancer syndromes: Important concepts for the primary care physician. Postgraduate Med. J. 2001, 77, 11–15. [Google Scholar] [CrossRef]
  79. Wiese, D.A.; Thaiwong, T.; Yuzbasiyan-Gurkan, V.; Kiupel, M. Feline mammary basal-like adenocarcinomas: A potential model for human triple-negative breast cancer (TNBC) with basal-like subtype. BMC Cancer 2013, 13, 403. [Google Scholar] [CrossRef] [PubMed]
  80. Beha, G.; Muscatello, L.V.; Brunetti, B.; Asproni, P.; Millanta, F.; Poli, A.; Benazzi, C.; Sarli, G. Molecular phenotype of primary mammary tumours and distant metastases in female dogs and cats. J. Compar. Pathol. 2014, 150, 194–197. [Google Scholar] [CrossRef] [PubMed]
  81. Brunetti, B.; Asproni, P.; Beha, G.; Muscatello, L.V.; Millanta, F.; Benazzi, C.; Sarli, G. Molecular phenotype in mammary tumours of queens: Correlation between primary tumour and lymph node metastasis. J. Compar. Pathol. 2013, 148, 206–213. [Google Scholar] [CrossRef] [PubMed]
  82. Martin de las Mulas, J.; Van Niel, M.; Millán, Y.; Ordás, J.; Blankenstein, M.A.; Van Mil, F.; Misdorp, W. Progesterone receptors in normal, dysplastic and tumourous feline mammary glands. Comparison with oestrogen receptors status. Res. Vet. Sci. 2002, 72, 153–161. [Google Scholar] [CrossRef] [PubMed]
  83. Millanta, F.; Calandrella, M.; Vannozzi, I.; Poli, A. Steroid hormone receptors in normal, dysplastic and neoplastic feline mammary tissues and their prognostic significance. Vet. Rec. 2006, 158, 821–824. [Google Scholar] [CrossRef] [PubMed]
  84. Caliari, D.; Zappulli, V.; Rasotto, R.; Cardazzo, B.; Frassineti, F.; Goldschmidt, M.H.; Castagnaro, M. Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer. BMC Vet. Res. 2014, 10, 185. [Google Scholar] [CrossRef] [PubMed]
  85. Carlson, R.W.; Allred, D.C.; Anderson, B.O.; Burstein, H.J.; Carter, W.B.; Edge, S.B.; Erban, J.K.; Farrar, W.B.; Goldstein, L.J.; Gradishar, W.J.; et al. Breast cancer. Clinical practice guidelines in oncology. J. Nat. Compr. Cancer Network 2009, 7, 122–192. [Google Scholar]
  86. Millanta, F.; Calandrella, M.; Citi, S.; Della Santa, D.; Poli, A. Overexpression of HER-2 in feline invasive mammary carcinomas: An immunohistochemical survey and evaluation of its prognostic potential. Vet. Pathol. 2005, 42, 30–34. [Google Scholar] [CrossRef] [PubMed]
  87. Rasotto, R.; Caliari, D.; Castagnaro, M.; Zanetti, R.; Zappulli, V. An immunohistochemical study of HER-2 expression in feline mammary tumours. J. Compar. Pathol. 2011, 144, 170–179. [Google Scholar] [CrossRef] [PubMed]
  88. Soares, M.; Correia, J.; Rodrigues, P.; Simões, M.; de Matos, A.; Ferreira, F. Feline HER2 protein expression levels and gene status in feline mammary carcinoma: Optimization of immunohistochemistry (IHC) and in situ hybridization (ISH) techniques. Microsc. Microanal. 2013, 19, 876–882. [Google Scholar] [CrossRef] [PubMed]
  89. Winston, J.; Craft, D.M.; Scase, T.J.; Bergman, P.J. Immunohistochemical detection of HER-2/neu expression in spontaneous feline mammary tumours. Vet. Compar. Oncol. 2005, 3, 8–15. [Google Scholar] [CrossRef] [PubMed]
  90. Maniscalco, L.; Iussich, S.; de Las Mulas, J.M.; Millán, Y.; Biolatti, B.; Sasaki, N.; Nakagawa, T.; De Maria, R. Activation of AKT in feline mammary carcinoma: A new prognostic factor for feline mammary tumours. Vet. J. 2012, 191, 65–71. [Google Scholar] [CrossRef] [PubMed]
  91. Gibson, H.M.; Veenstra, J.; Jones, R.F.; Vaishampayan, U.; Sauerbrey, M.; Bepler, G.; Lum, L.; Reyes, J.; Weise, A.; Wei, W.Z. Induction of HER2 Immunity in Outbred Domestic Cats by DNA Electrovaccination. Cancer Immunol. Res. 2015. Available online: http://www.biomedcentral.com/1471-2407/13/218 (accessed on 25 June 2015). [CrossRef] [PubMed]
  92. Santos, S.; Baptista, C.S.; Abreu, R.M.; Bastos, E.; Amorim, I.; Gut, I.G.; Gärtner, F.; Chaves, R. ERBB2 in cat mammary neoplasias disclosed a positive correlation between RNA and protein low expression levels: a model for erbB-2 negative human breast cancer. PLoS ONE. 2013, 8. Available online: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083673 (accessed on 25 June 2015). [CrossRef] [PubMed]
  93. Malhotra, G.K.; Zhao, X.; Band, H.; Band, V. Histological, molecular and functional subtypes of breast cancers. Cancer Biol. Therapy 2010, 10, 955–960. [Google Scholar] [CrossRef]
  94. Morrison, W.B. Inflammation and cancer: A comparative view. J. Vet. Intern. Med. 2012, 26, 18–31. [Google Scholar] [CrossRef] [PubMed]
  95. Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell 2010, 140, 883–899. [Google Scholar] [CrossRef] [PubMed]
  96. Vascellari, M.; Melchiotti, E.; Bozza, M.A.; Mutinelli, F. Fibrosarcomas at presumed sites of injection in dogs: Characteristics and comparison with non-vaccination site fibrosarcomas and feline post-vaccinal fibrosarcomas. J. Vet. Med. A Physiol. Pathol. Clin. Med. 2003, 50, 286–291. [Google Scholar] [CrossRef] [PubMed]
  97. Vascellari, M.; Melchiotti, E.; Mutinelli, F. Fibrosarcoma with typical features of postinjection sarcoma at site of microchip implant in a dog: Histologic and immunohistochemical study. Vet. Pathol. 2006, 43, 545–548. [Google Scholar] [CrossRef] [PubMed]
  98. Vascellari, M.; Mutinelli, F.; Cossettini, R.; Altinier, E. Liposarcoma at the site of an implanted microchip in a dog. Vet. J. 2004, 168, 188–190. [Google Scholar] [CrossRef]
  99. Murray, J. Vaccine injection-site sarcoma in a ferret. J. Amer. Vet. Med. Assoc. 1998, 213, 955. [Google Scholar]
  100. Keel, S.B.; Jaffe, K.A.; Petur Nielsen, G.; Rosenberg, A.E. Orthopaedic implant-related sarcoma: A study of twelve cases. Modern Pathol. 2001, 14, 969–977. [Google Scholar] [CrossRef] [PubMed]
  101. Liptak, J.M.; Forrest, L.J. Soft Tissue Sarcomas. In Withrow and MacEwen’s Small Animal Clinical Oncology, 5th ed.; Withrow, S.J., Vail, D.M., Page, R.L., Eds.; Elsevier Saunders: St Louis, MO, USA, 2012; pp. 356–380. [Google Scholar]
  102. Dean, R.S.; Pfeiffer, D.U.; Adams, V.J. The incidence of feline injection site sarcomas in the United Kingdom. BMC Vet. Res. 2013, 9, 17. [Google Scholar] [CrossRef] [PubMed]
  103. Doddy, F.D.; Glickman, L.T.; Glickman, N.W.; Janovitz, E.B. Feline fibrosarcomas at vaccination sites and non-vaccination sites. J. Compar. Pathol. 1996, 114, 165–174. [Google Scholar] [CrossRef]
  104. Couto, S.S.; Griffey, S.M.; Duarte, P.C.; Madewell, B.R. Feline vaccine-associated fibrosarcoma: Morphologic distinctions. Vet. Pathol. 2002, 39, 33–41. [Google Scholar] [CrossRef] [PubMed]
  105. Hendrick, M.J.; Brooks, J.J. Postvaccinal Sarcomas in the Cat: Histology and Immunohistochemistry. Vet. Pathol. 1994, 31, 126–129. [Google Scholar] [CrossRef] [PubMed]
  106. Aberdein, D.; Munday, J.S.; Dyer, C.B.; Knight, C.G.; French, A.F.; Gibson, I.R. Comparison of the histology and immunohistochemistry of vaccination-site and non-vaccination-site sarcomas from cats in New Zealand. New Zealand Vet. J. 2007, 55, 203–207. [Google Scholar] [CrossRef] [PubMed]
  107. Dubielzig, R.R.; Everitt, J.; Shadduck, J.A.; Albert, D.M. Clinical and morphologic features of post-traumatic ocular sarcomas in cats. Vet. Pathol. 1990, 27, 62–65. [Google Scholar] [CrossRef] [PubMed]
  108. Douglas, J.L.; Gustin, J.K.; Moses, A.V.; Dezube, B.J.; Pantanowitz, L. Kaposi Sarcoma Pathogenesis: A Triad of Viral Infection, Oncogenesis and Chronic Inflammation. Transl. Biomed. 2010, 1. Available online: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3472629/ (accessed on 25 June 2015).
  109. Jourdier, T.M.; Moste, C.; Bonnet, M.C.; Delisle, F.; Tafani, J.P.; Devauchelle, P.; Tartaglia, J.; Moingeon, P. Local immunotherapy of spontaneous feline fibrosarcomas using recombinant poxviruses expressing interleukin 2 (IL2). Gene Therapy 2003, 10, 2126–2132. [Google Scholar] [CrossRef] [PubMed]
  110. Banerji, N.; Kanjilal, S. Somatic alterations of the p53 tumor suppressor gene in vaccine-associated feline sarcoma. Amer. J. Vet. Res. 2006, 67, 1766–1772. [Google Scholar] [CrossRef] [PubMed]
  111. McEntee, M.C.; Page, R.L. Feline vaccine-associated sarcomas. J. Vet. Intern. Med. 2001, 15, 176–182. [Google Scholar] [CrossRef] [PubMed]
  112. Tannehill-Gregg, S.; Kergosien, E.; Rosol, T.J. Feline head and neck squamous cell carcinoma cell line: characterization, production of parathyroid hormone-related protein, and regulation by transforming growth factor-beta. In Vitro Cell. Dev. Biol. Anim. 2001, 37, 676–683. [Google Scholar] [CrossRef]
  113. Modiano, J.F.; Kokai, Y.; Weiner, D.B.; Pykett, M.J.; Nowell, P.C.; Lyttle, C.R. Progesterone augments proliferation induced by epidermal growth factor in a feline mammary adenocarcinoma cell line. J. Cell. Biochem. 1991, 45, 196–206. [Google Scholar] [CrossRef] [PubMed]
  114. Norval, M.; Maingay, J.; Else, R.W. Characteristics of a feline mammary carcinoma cell line. Res. Vet. Sci. 1985, 39, 157–164. [Google Scholar] [PubMed]
  115. Uyama, R.; Hong, S.H.; Nakagawa, T.; Yazawa, M.; Kadosawa, T.; Mochizuki, M.; Tsujimoto, H.; Nishimura, R.; Sasaki, N. Establishment and characterization of eight feline mammary adenocarcinoma cell lines. J. Vet. Med. Sci. 2005, 67, 1273–1276. [Google Scholar] [CrossRef] [PubMed]
  116. Takauji, S.R.; Watanabe, M.; Uyama, R.; Nakagawa, T.; Miyajima, N.; Mochizuki, M.; Nishimura, R.; Sugano, S.; Sasaki, N. Expression and subcellular localization of E-cadherin, alpha-catenin, and beta-catenin in 8 feline mammary tumor cell lines. J. Vet. Med. Sci. 2007, 69, 831–834. [Google Scholar] [CrossRef] [PubMed]
  117. Muleya, J.S.; Nakaichi, M.; Sugahara, J.; Taura, Y.; Murata, T.; Nakama, S. Establishment and characterization of a new cell line derived from feline mammary tumor. J. Vet. Med. Sci. 1998, 60, 931–935. [Google Scholar] [CrossRef] [PubMed]
  118. Muleya, J.S.; Nakaichi, M.; Taura, Y.; Yamaguchi, R.; Nakama, S. In-vitro anti-proliferative effects of some anti-tumour drugs on feline mammary tumour cell lines. Res. Vet. Sci. 1999, 66, 169–174. [Google Scholar] [CrossRef] [PubMed]
  119. Minke, J.M.; Schuuring, E.; van den Berghe, R.; Stolwijk, J.A.; Boonstra, J.; Cornelisse, C.; Hilkens, J.; Misdorp, W. Isolation of two distinct epithelial cell lines from a single feline mammary carcinoma with different tumorigenic potential in nude mice and expressing different levels of epidermal growth factor receptors. Cancer Res. 1991, 51, 4028–4037. [Google Scholar] [PubMed]
  120. Adelfinger, M.; Gentschev, I.; Grimm de Guibert, J.; Weibel, S.; Langbein-Laugwitz, J.; Härtl, B.; Murua Escobar, H.; Chen, N.G.; Aguilar, R.J.; Yu, Y.A.; et al. Evaluation of a new recombinant oncolytic vaccinia virus strain GLV-5b451 for feline mammary carcinoma therapy. PLoS ONE. 2014, 9. Available online: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104337 (accessed on 25 June 2015). [CrossRef] [PubMed]
  121. Williams, L.E.; Banerji, N.; Klausner, J.S.; Kapur, V.; Kanjilal, S. Establishment of two vaccine-associated feline sarcoma cell lines and determination of in vitro chemosensitivity to doxorubicin and mitoxantrone. Amer. J. Vet. Res. 2001, 62, 1354–1357. [Google Scholar] [CrossRef] [PubMed]
  122. Banerji, N.; Li, X.; Klausner, J.S.; Kapur, V.; Kanjilal, S. Evaluation of in vitro chemosensitivity of vaccine-associated feline sarcoma cell lines to vincristine and paclitaxel. Amer. J. Vet. Res. 2002, 63, 728–732. [Google Scholar] [CrossRef] [PubMed]
  123. Katayama, R.; Huelsmeyer, M.K.; Marr, A.K.; Kurzman, I.D.; Thamm, D.H.; Vail, D.M. Imatinib mesylate inhibits platelet-derived growth factor activity and increases chemosensitivity in feline vaccine-associated sarcoma. Cancer Chemother. Pharmacol. 2004, 54, 25–33. [Google Scholar] [CrossRef] [PubMed]
  124. Lawrence, J.; Saba, C.; Gogal, R., Jr.; Lamberth, O.; Vandenplas, M.L.; Hurley, D.J.; Dubreuil, P.; Dobbin, K.; Turek, M. Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Vet. Compar. Oncol. 2012, 10, 143–154. [Google Scholar] [CrossRef] [PubMed]
Back to TopTop