Metallothionein Expression in Canine and Feline Mammary and Melanotic Tumours

Dincer, Z.; Jasani, Bharat; Haywood, S.; Mullins, J. E.; Fuentealba, I. C.

doi:10.1053/jcpa.2001.0488

Cited by 19 publications

(16 citation statements)

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“…Metallothionein (MT) is a low molecular weight protein (10 kDa) with a high cysteine content (30%), exhibiting selective binding affinity for Zn, Cu and other group II heavy metals. MT is thought to play essential roles in Zn and Cu metabolism, heavy metal transport (particularly in copper-loaded animals), and to protect cells from oxidative stress [2]. According to previous reports, in dogs, MT immunoreactivity was observed in the central nervous system, liver, kidney etc., and MT cDNA obtained from the liver of a cadmium-treated beagle was cloned and sequenced [11,21].…”

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“…In dogs and cats, there are reports of the immunohistochemical study of the expression of proteins associated with multidrug resistance in mast cell tumor, mammary gland tumor and melanocytic tumor, but there are no reports about canine and feline primary pulmonary carcinoma [2,15]. The aim of this study was to investigate the expression of PGP, MRP, LRP and MT using immunohistochemical methods in canine and feline primary pulmonary carcinoma, and to estimate the effectiveness to chemotherapy.…”

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Immunohistochemical Detection of Proteins Associated with Multidrug Resistance to Anti-Cancer Drugs in Canine and Feline Primary Pulmonary Carcinoma

et al. 2010

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ABSTRACT. Fifty-two canine and eighteen feline primary pulmonary carcinomas were evaluated immunohistochemically for the expression of proteins associated with multidrug resistance to anti-cancer drugs. P-glycoprotein (PGP), multidrug resistance-related protein (MRP) and lung resistance-related protein (LRP) expression were frequently observed in neoplastic cells of all carcinoma types, and metallothionein (MT) expression was observed in about half of each carcinoma type. Furthermore, overlapping expression was detected in all positive cases. These results indicate that most canine and feline primary pulmonary carcinomas may have strong multidrug resistance, which is related to the PGP, MRP, LRP or MT expression. It might be difficult to treat canine and feline primary pulmonary carcinomas using anti-cancer drugs because of multidrug resistance.KEY WORDS: immunohistochemistry, lung resistance-related protein, metallothionein, multidrug resistance-related protein, P-glycoprotein.J. Vet. Med. Sci. 72 (5): [665][666][667][668] 2010 Human primary pulmonary carcinoma is divided into 2 groups; small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Surgical resection is not suitable for SCLC because of metastasis at the time of diagnosis in many cases; therefore, chemotherapy is recommended generally. For NSCLC, however, including adenocarcinoma, adenosquamous carcinoma and squamous cell carcinoma, chemotherapy is less effective; therefore, surgical resection is recommended generally [12]. Primary pulmonary tumors in domestic animals are uncommon to extremely rare, with a prevalence of 0.1-0.9% in dogs, a little higher than in cats [23]. In the treatment of canine and feline primary pulmonary carcinoma, surgical resection is recommended [18], but to reduce the risk of local recurrence and metastasis, adjuvant chemotherapy is required similarly to the treatment for human NSCLC. P-glycoprotein (PGP), a 150-170 kDa plasma membrane protein, belongs to the ATP binding cassette (ABC) superfamily of transporter proteins, and can extrude a range of hydrophobic anti-cancer drugs from the cell [20]. Overexpression of PGP is associated with resistance to different types of anti-cancer drugs (e.g. daunorubicin, doxorubicin, mitoxantrone, etoposide, teniposide, vinblastine, vincristine, mitomycin C, paclitaxel, actinomycin D and topotecan) [6]. Multidrug resistance-related protein (MRP), which belongs to the ABC superfamily as PGP, is a 190 kDa membrane-bound glycoprotein. MRP probably works by direct extrusion of cytotoxic drugs from the cell and/or by mediating sequestration of the drugs into intracellular compartments, both leading to a reduction in effective intracellular drug concentrations [16]. Overexpression of MRP is associated with resistance to doxorubicin, vincristine, actinomycin D, etoposide and colchicine [7,22]. Lung resistance-related protein (LRP) is a 110 kDa protein found in multidrug-resistant cell lines not expressing PGP. LRP is the main component of vault protein, and plays a role in ...

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Immunohistochemical Detection of Proteins Associated with Multidrug Resistance to Anti-Cancer Drugs in Canine and Feline Primary Pulmonary Carcinoma

et al. 2010

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“…The expression of MT fluctuates during tumour growth, and in some human tumours (breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid, and urinary bladder tumours) the level of MT is positively correlated with the proliferation rate and the malignancy grade (Gumulec et al 2014). On the other hand, a complete lack of MT expression was observed in some human colo-rectal adenocarcinomas, what was linked to spontaneous and mutagenic DNA damage (Dincer et al 2001). In the evaluated canine EMPs, the expression of MT was variable, but usually low to moderate, in contrast to the feline EMPs, where MT expression was absent or low despite the type and tumour localization.…”

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confidence: 99%

“…The metal-bound MT shields DNA from damaging agents. The metal-free MT interacts with the tumour suppressor protein p53, leading to its inactivation, followed by increased cellular proliferation (Dincer et al 2001, Martano et al 2012. The studies of MT expression have been limited to canine apocrine gland tumours, mammary gland tumours, melanocytic tumours, and primary pulmonary carcinomas.…”

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Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas

Mikiewicz¹,

Otrocka-Domagała²,

Paździor-Czapula³

et al. 2016

Polish Journal of Veterinary Sciences

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The aim of the study was the evaluation of morphology and immunophenotype of canine (19 cases) and feline (7 cases) extramedullary plasmacytomas. Tumours, located in skin, oral cavity and spleen were surgically excised, fixed and processed for histopathology and immunohistochemistry (CD79α, CD18, proliferating cell nuclear antigen, metallothionein). Histologically, tumours were classified into mature, cleaved, asynchronous, polymorphous blastic, hyalin, or monomorphous blastic type. All evaluated tumours showed cytoplasmic expression of CD79α antigen. The expression of CD18 was observed in canine cutaneous and splenic tumours. In canine tumours expression of metallothionein was low to moderate, while in feline plasmacytomas -absent or low. In canine tumours, the mitotic index and proliferating cell nuclear antigen index were positively correlated with the expression of metallothionein. In feline tumours no correlation between mitotic index, proliferating cell nuclear antigen and metallothionein was found. This is the first study describing expression of metallothionein in canine and feline extramedullary plasmacytoma.

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Comparative Oncology of Skin Cancer

Gordon

2013

Skin Cancer

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Cancer is the leading cause of death in people from 45 to 65 years of age and the leading cause of death for geriatric pets [ 1,2 ] . The annual incidence of skin cancer in dogs and cats is estimated to be 90.4 and 34.7 per 100,000 pets at risk [ 3 ] . This annual incidence is high compared to humans with an annual incidence of only 5.2 per 100,000 people at risk [ 1,[4][5][6] . Studying this animal population with skin cancer provides an opportunity to improve our knowledge about the biology, epidemiology, pathogenesis, and treatment of skin cancer across species, contributing to advances in human and animal health through a comparative oncology approach. The Study of Skin Cancer and Advantages of the Comparative Oncology ApproachThe complex biology and therapeutic challenges associated with skin cancer necessitates continued research. Considerable knowledge about skin cancer comes from clinical experience and clinical studies of human patients. As with all cancer research, in vitro and in vivo studies also contribute to our knowledge and guide decisions that will hopefully lead to new options and breakthroughs in the treatment of skin cancer. Progress can be slow, and approaches that seem promising based on in vitro and in vivo studies frequently do not end up translating into signi fi cant improvements when attempted in the clinic. These approaches are still a valuable and necessary component of skin cancer research. Newer mouse models of cancer and advanced in vitro research techniques will continue to improve our understanding of skin cancer. Developments in the fi elds of surgical oncology, radiation oncology, and drug development toward treatments that more effectively target skin cancer while sparing normal tissues improve our ability to effectively manage patients with this disease. Comparative Oncology of Skin Cancer Ira Gordon Key PointsNaturally occurring skin cancers of • companion animals can serve as useful models of our understanding of these diseases in people.The most common skin tumors in dogs • include mast cell tumor, lipoma, sebaceous gland tumor, histiocytoma, squamous cell carcinoma, melanoma, fi brosarcoma, and basal cell tumor. The most common skin tumors in cats • include basal cell tumor, mast cell tumor, fi brosarcoma, squamous cell carcinoma, and sebaceous gland tumor.

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Metallothionein Expression in Canine and Feline Mammary and Melanotic Tumours

Cited by 19 publications

References 29 publications

Immunohistochemical Detection of Proteins Associated with Multidrug Resistance to Anti-Cancer Drugs in Canine and Feline Primary Pulmonary Carcinoma

Immunohistochemical Detection of Proteins Associated with Multidrug Resistance to Anti-Cancer Drugs in Canine and Feline Primary Pulmonary Carcinoma

Morphology and immunoreactivity of canine and feline extramedullary plasmacytomas

Comparative Oncology of Skin Cancer

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