DNA damage in canine transmissible venereal tumor cells

O Tumor Venéreo Transmissível (TVT) tem sido classificado de acordo com o tipo celular predominante da seguinte forma: linfocitóide, plasmocitóide e misto. Vários graus de agressividade com grande variedade de comportamento biológico, têm sido descritos de acordo com as morfologias das células do TVT. O presente estudo teve como objectivo investigar o nível de danos no DNA nos três tipos de células do TVT, visando uma melhor compreensão dos mecanismos relacionados com a agressividade dessa neoplasia. Um total de 35 cães, sem restrição quanto à idade, sexo ou raça, e com diagnóstico clínico e citológico de TVT foram avaliados. Amostras de células foram obtidas a partir de 35 tumores, por aspiração com agulha fina, e realizada citologia e análise dos danos no DNA, pelo Ensaio Cometa. Dos 35 casos de TVT, 12 (34,3%) foram plasmocitóide, 11 (31,4%) linfocitóide, e 12 (34,3%) misto. Estatísticamente (p <0,05) o TVT linfocitóide apresentou maior nível de danos no DNA quando comparado com os outros dois tipos.

Reactivity of p53 protein in canine transmissible venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

INTRAOCULAR TRANSMISSIBLE VENEREAL TUMOR IN A DOG

Tumor venéreo transmissível (TVT) é uma neoplasia de células redondas que acomete a mucosa genital externa de cães, machos e fêmeas. A transmissão decorre da implantação de células tumorais durante o coito, brigas ou interações entre animais portadores e susceptíveis. Existem relatos referindo-se a localizações atípicas do TVT, mas metástases raramente ocorrem. O presente relato descreve um caso incomum de TVT, com acometimento intra-ocular e metástases nos linfonodos ingüinais, num cão Terrier Brasileiro, com seis anos de idade. O animal apresentava massas anormais de tecido no olho direito, extremidade do pênis e aumento de volume de linfonodos da região ingüinal. A histopatologia do globo ocular e as citologias da massa peniana e dos nódulos subcutâneos evidenciaram aspectos citológicos semelhantes, caracterizados por células redondas com núcleo grande e nucléolo proeminente localizado centralmente. O citoplasma apresentou-se pálido e com presença de vacúolos pequenos e arredondados. O diagnóstico de TVT com acometimento intra-ocular e metástases em linfonodos foi baseado nos achados clínicos, citológicos e histopatológicos.

Spontaneous canine transmissible venereal tumor: cell morphology and influence on P-glycoprotein expression

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Spontaneous canine transmissible venereal tumor: association between different phenotypes and the insertion LINE-1/c-myc

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Expression of P-glycoprotein, multidrug resistance-associated protein, glutathione-S-transferase pi and p53 in canine transmissible venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Leishmania sp. amastigotes identification in canine transmissible venereal tumor

Leishmaniasis is a vector-borne disease with Leishmania chagasi being the etiological agent of canine visceral leishmaniasis in South America. Canine venereal tumor is a transplantable round cell tumor of histiocytic origin which is mostly observed in sexually active male and female intact dogs. It has been shown that Leishmania amastigotes have higher tropism for the canine male genital tract tissues and venereal leishmaniasis transmission has been documented in dogs but, to date, a canine venereal tumor-dependent transmission route has not been fully demonstrated. In this report, a 10-year-old, mixed breed, intact female dog presented a vaginal venereal transmissible tumor but no other clinical abnormalities otherwise. Unexpectedly, tumor tissue imprint smears examination revealed Leishmania sp. amastigotes within infiltrating macrophages. In addition to the cytological direct identification, the protozoan was confirmed within the neoplastic tissue by means of immunohistochemistry and polymerase chain reaction. This report illustrates an asymptomatic Leishmania sp. infection that may have started on or from the canine venereal tumor tissue, the latter option further supporting previous evidence of such an alternative vector-independent route of transmission for canine visceral leishmaniasis in areas where these diseases coexist.

Histopathological and cytological analysis of transmissible venereal tumor in dogs after two treatment protocols

The transmissible venereal tumor (TVT) is a contagious neoplasm of round cells that frequently affect dogs. The treatment consists of chemotherapy being more effective the vincristine alone, however the resistance emergence to this agent due multidrug resistance of the P-glycoprotein (P-gp), a transporter protein encoded by the MDR1 gene, has been taking the association with other drugs. Recent studies demonstrated the antitumoral effect of the avermectins when associated to the vincristine in the treatment of some neoplasms. Therefore, the objective of the present study was to compare the effectiveness of standard treatment of TVT with vincristine only as compared to combined treatment with vincristine and ivermectin, evaluated through number of applications of the two protocols, histopathological and cytological analysis from 50 dogs diagnosed with TVT during the period of 2007 to 2010. The combined protocol significant reduces the number of applications and cytological and histopathological findings collaborate with the hypothesis that the combination of vincristine and ivermectin promotes faster healing than the use of vincristine alone. Combination treatment with vincristine and ivermectin could be in the future an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, simultaneously reducing the cost of TVT treatment and a faster recovery of the dog.

Tumor venéreo transmissível com metástases cutâneas em um cão transmissible venereal

O tumor venéreo transmissível é diagnosticado, na maioria das vezes, em animais jovens, sadios e sexualmente ativos. Acomete, comumente, a genitália externa. Metástases, apesar de incomuns, ocorrem. O presente trabalho relata um caso de tumor venéreo transmissível na glande peniana com disseminação para a pele das regiões abdominal e inguinal.

Canine transmissible venereal tumors: Aspects related to programmed cell death

Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by the physical transfer of viable tumor cells by direct contact with injured skin and/or mucous tissue. These cells can transpose across histocompatibility barriers into unrelated hosts. This review focuses on the biology of apoptosis and the interaction of proteins involved in this process, as well as p53, p63 and the antiapoptotic protein Bcl-2. As such, this disease offer unique opportunity to study the biology of transplantable tumours and the interaction of proteins involved in apoptosis process and the prognosis of CTVT.

Immunohistochemical expression of B and T-lymphocytes and TGF-beta in experimentally transplanted canine venereal tumor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison against 186 canid whole genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic drivers of clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.

Disseminated Transmissible Venereal Tumour Associated With Leishmaniasis in a Dog

This report addresses an atypical transmissible venereal tumour in an 8-year-old bitch that was pluriparous and seropositive for leishmaniasis. There were ascites and a serosanguineous discharge from the vulva, but no lesions on the external genital mucosa. An aspirate of the peritoneal fluid showed mononuclear round cells characteristic of transmissible venereal tumour (TVT). Exploratory laparotomy revealed light red, granulomatous structures in the peritoneum, omentum, spleen, liver and uterine horns. Cytological and histopathological tests confirmed the diagnosis of intra-abdominal TVT. Dissemination of the TVT to several organs inside the abdominal cavity probably resulted from immunosuppression caused by leishmaniasis, which favoured the presence and aggressiveness of TVT.

Tumor venéreo transmissível espontâneo canino: a inserção do transposon line-1 no gene C-MYC e os critérios de malignidade

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)