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DNA damage (tail intensity) in canine Trasmissible Veneral Tumor (TVT) cells of different morphology subtypes.
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Canine transmissible venereal tumor (CTVT) is a tumor that commonly occurs in genital and extragenital sites of both genders. Long Interspersed Nuclear Elements (LINE-1) retrotransposon has the pivotal role in allogenic transfection amongst uncontrolled dog population. In the study, it is aimed to evaluate pathomorphological, immunohistochemical an...
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... O tipo de linfócito foi encontrado com mais frequência nas localizações genitais. Outros estudos realizados posteriormente apóiam o estudo anterior; apoiaram que casos de TVT com maior nível de agressividade apresentavam tumores predominantemente do tipo plasmocitóide (Amaral et al., 2011;Bassani-Silva et al., 2007;Gaspar et al., 2011). ...
... Vários testes foram realizados para explicar a malignidade e a capacidade de metástases do tipo plasmocitóide, como a eletroforese em gel de célula única, também chamada de "teste de cometa", que é uma técnica visual para analisar e medir as quebras de DNA nas células de mamíferos. Estudos mostraram que casos de TVT com morfologia plasmocitoide exibiam menos quebras de DNA, o que seria um mecanismo ilusório para a remoção de células tumorais (Amaral et al., 2007;Amaral et al., 2011). ...
O tumor venéreo transmissível canino é um dos poucos tipos de tumores contagiosos descritos em mamíferos. É transplantado como um aloenxerto de células viáveis na mucosa e/ou pele, onde desencadeia um processo imunológico que varia de acordo com o estágio de desenvolvimento. O TVT possui 4 fases; a fase de progressão (P) caracterizada pela evasão da barreira da histocompatibilidade e a resposta imune por mecanismos imunossupressores, seguida pela fase de estagnação (E) na qual ocorre um processo de estase entre o tumor e o sistema imunológico que permite a remodelação do tecido danificado, na fase de regressão (R), o evento principal é a reativação da resposta imune mediada pela infiltração de linfócitos T e citocinas pró-inflamatórias como a interleucina IL-6 e interferon gama (IFN-γ) , para a remoção do tumor. A fase de metástase (M), ou disseminação do tumor, se desenvolve em hospedeiros não imunocompetentes. Esta revisão descreve em detalhes os processos imunológicos realizados em cada fase.
... According to STOCKMANN et al. (2011) overexpression of Bcl-2 occurs independent of the stage of tumor development and this overexpression would promote the acquisition of functions in the tumor, which are associated with progression and survival. Similarly, AMARAL et al. (2011) showed that CTVTs with a lower degree of aggressiveness have a high apoptotic index and may present a better prognosis. ...
... STOCKMANN et al. (2011) still suggested that its overexpression would promote the acquisition of characteristics in the tumor, associated with progression and survival. Likewise, AMARAL et al. (2011) highlighted that CTVTs with a lower degree of aggressiveness has a high apoptotic index, and may even have a better prognosis. The decrease in BCL-2 expression was observed in three samples, as well as the decrease in BCL-xL in thirteen samples. ...
Canine transmissible venereal tumor (CTVT) is a transmissible neoplasm, which spreads naturally between dogs through the halogenic transfer of tumor cells, mainly during coitus. It is the oldest known tumoral lineage in nature and reports on gene mutations have been extended. Also, this tumor shares several genetic mutations with some cancers in humans, among them lung carcinomas, melanoma, prostate, breast, among other cancers. Thus, expression of tumor suppressor genes such as TP53, P21, and apoptosis-related genes such as BAX, BCL-2, and BCL-xL, both in vivo and in vitro (primary cell culture) were quantified. In the present study, the comparison of gene expression, the TP53 gene, in most cases, was shown to be high in the majority of tissues (65%) and primary cell culture (100%), while BCL-2, BCL-xL, and BAX presented variation among the animals analyzed. Moreover, in these situations, the results suggested that the apoptotic regulation of these genes did not occur for TP53. The P21 gene was shown to be mostly normal (70%); although, absence (6%) and underexpressions (24%) were also observed. Statistical analysis of the BCL-xL gene demonstrated significant differences between the tissues of the animals when compared to the cell cultures; however, to the other genes, no statistical difference was observed between the groups. Preliminarily, the results suggested the presence of alterations in the gene expressions of the TP53, P21, BAX, BCL-2 and BCL-xL leading to loss of function in these genes, which affect the tumorigenesis of CTVT.
... in basal cell carcinoma (47), and resulting in improved patient survival in human breast carcinoma (25). Furthermore, a higher rate of apoptosis was related to the less aggressive behavior in CTVT cases (48). According to this information, it may imply that Bcl-2 overexpression is related to tumor progression and tumor survival factor in tumor cells (49). ...
... However, a lower ABCB1 expression has been reported, meaning this situation is still under controversy. The low expression of ABCB1 after treatment may require a higher level of chemotherapeutic induction (48). From CTVT studies, ABCB1, MRP1, and MRP2 have been studied, but there is no data on ABCG2 expression. ...
Background: Vincristine (VCR) is a mono-chemotherapy for canine transmissible venereal tumor (CTVT). L-asparaginase (LAP) is usually used in combination with other drugs. Previously, LAP-VCR protocol was applied for the CTVT-VCR-resistant cases. However, there were a few reports about using this protocol since the first visit.
Aims: To firstly investigate the effectiveness of combining chemotherapy (Vincristine and L-asparaginase, VCR-LAP) in normal CTVT case. Secondly, to compare this protocol with the conventional (Vincristine, VCR) protocol before and during treatment in 24 CTVT dogs.
Materials and Methods: Clinical signs, tumor relative volume, and histopathological change [amount of CTVT cells, tumor-infiltrating lymphocytes (TILs), TILs/CTVT ratio, collagen area, and Ki-67 proliferative index (PI)] were the treatment evaluation parameters. Moreover, transcriptome analysis of apoptotic (Bcl-2, Bax), drug-resistant genes (ABCB1, ABCG2), and BCL-2 and BAX expression were also included.
Results: Both protocols gave the decreased tumor volume, increased TILs/CTVT ratios and collagen area in the mass. Interestingly, the combination protocol decreased treatment time. There were two resistant cases after treatment with VCR. The expression of Bcl-2 and Bax were decreased, and this may indicate the better response after treatment. Moreover, both drug resistant genes did not increase after treatment.
Conclusion: The main finding of this study is that the combination protocol did not only decrease treatment duration time but also gave the effectiveness of treatment outcomes in CTVT cases. Therefore, the application of the new protocol could be used by the field practitioners.
... However, many questions regarding its biological behavior remain unresolved. It is known that some CTVTs present with varying degrees of aggressiveness (Amaral et al., 2011) and resistance to chemotherapy (Florez et al., 2016). Usually, the more severe cases result in metastasis and dissemination of the tumor. ...
... Initially, a cytopathological analysis of the tumors revealed that CTVT presents different cytomorphological types, which are currently classified as plasmacytoid and lymphocytoid; we hypothesized that there is a correlation between these cytomorphological types and the degree of tumor aggressiveness Montoya et al., 2012). Subsequently, it was established and supported by several studies that CTVT cases with a higher level of aggressiveness had tumors consisting of predominantly plasmacytoid cells Gaspar et al., 2010;Amaral et al., 2011). Moreover, single-cell gel electrophoresis, a visual technique to analyze and measure DNA breaks in mammalian cells that is also known as the "comet test", demonstrated that CTVT cases with a plasmacytoid morphology exhibited fewer DNA breaks, which is probably an evasive mechanism for the elimination of tumor cells (Amaral et al., 2011). ...
... Subsequently, it was established and supported by several studies that CTVT cases with a higher level of aggressiveness had tumors consisting of predominantly plasmacytoid cells Gaspar et al., 2010;Amaral et al., 2011). Moreover, single-cell gel electrophoresis, a visual technique to analyze and measure DNA breaks in mammalian cells that is also known as the "comet test", demonstrated that CTVT cases with a plasmacytoid morphology exhibited fewer DNA breaks, which is probably an evasive mechanism for the elimination of tumor cells (Amaral et al., 2011). Likewise, immunohistochemical studies (IHC) performed in CTVT cases revealed that the plasmacytoid morphology is associated with both high Ki-67 reactivity (Bassani-Silva et al., 2015) and an increased expression of P-Glycoprotein, indicating a higher mitotic potential and resistance to chemotherapy, respectively (Gaspar et al., 2010;Montoya et al., 2012). ...
CTVT; Chemotherapy; MDR-1; P-Glycoprotein
... In previous studies conducted at the Laboratory of Investigative Pathology of the College of Veterinary Medicine and Zootechny (FMVZ Botucatu), some TVT presented fewer DNA breaks (Amaral et al. 2011), larger nucleolar sizes (Amaral 2005) and high reactivity of Ki-67 (MBI-1). This points towards an intense proliferation of neoplastic cells (Gaspar 2005), higher rates of metastases ) and increased expression rates of p-glycoprotein (Gaspart et al. 2010). ...
with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3 and anti-CD79α antibodies has been used for characterization of primary cell culture in the transmissible venereal tumor (TVT). Samples for primary cell culture and immunohistochemistry assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To validate the immunochemical results in the primary cell culture of TVT, a chromosome count was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used. TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of 56 to 68. This is the first report on the use of immunocytochemical characterization in cell culture of TVT. Significant statistic difference between immunochemistry in tissue and culture cell was not established, what suggests that the use of this technique may provide greater certainty for the confirmation of tumors in the primary culture. This fact is particularly important because in vitro culture of tumor tissues has been increasingly used to provide quick access to drug efficacy and presents relevant information to identify potential response to anticancer medicine; so it is possible to understand the behavior of the tumor.
... In previous studies conducted at the Laboratory of Investigative Pathology of the College of Veterinary Medicine and Zootechny (FMVZ Botucatu), some TVT presented fewer DNA breaks (Amaral et al. 2011), larger nucleolar sizes (Amaral 2005) and high reactivity of Ki-67 (MBI-1). This points towards an intense proliferation of neoplastic cells (Gaspar 2005), higher rates of metastases ) and increased expression rates of p-glycoprotein (Gaspart et al. 2010). ...
Immunochemistry with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3
and anti-CD79α antibodies has been used for characterization of primary cell culture in the
transmissible venereal tumor (TVT). Samples for primary cell culture and immunohistochemistry
assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To
validate the immunochemical results in the primary cell culture of TVT, a chromosome count
was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used.
TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate
immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking
was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of
56 to 68. This is the first report on the use of immunocytochemical characterization in cell
culture of TVT. Significant statistic difference between immunochemistry in tissue and culture
cell was not established, what suggests that the use of this technique may provide greater
certainty for the confirmation of tumors in the primary culture. This fact is particularly important
because in vitro culture of tumor tissues has been increasingly used to provide quick
access to drug efficacy and presents relevant information to identify potential response to
anticancer medicine; so it is possible to understand the behavior of the tumor.
... 39 Similarly, Amaral et al. emphasise that less aggressive TVT have a high rate of apoptosis, which may lead to better prognosis. 40 Thus, culture studies have formidably increased the understanding of the pathogenesis of certain cancers, and provided a basis for developing new methods of tumour diagnosis and treatment. 41 As to TVT, the success of culturing has been described by other researchers, 42 -47 although few analyses were made in their studies. ...
Transmissible venereal tumour (TVT) generally presents different degrees of aggressiveness, which makes them unresponsive to conventional treatment protocols. This implies a progressive alteration of their biological profile. This study aimed to evaluate the cytotoxicity, cell survival, apoptosis and cell cycle alterations in TVT cell cultures subjected to treatment with vincristine. Similarly, it assessed possible implications of MDR-1, TP53, BCL-2, and BAX gene expressions in eight TVT primary cultures for both resistance to chemotherapy and biological behaviour. When comparing TVT cells receiving vincristine to those untreated, a statistical difference related to increased cytotoxicity and decreased survival rates, and alterations in G1 and S cell cycle phases were found but without detectable differences in apoptosis. Increased MDR-1 gene expression was observed after treatment. The groups did not differ statistically in relation to the TP53, BAX and BCL-2 genes. Although preliminary, the findings suggest that such augmented expression is related to tumour malignancy and chemotherapy resistance.
... It has been shown that TVTs with plasmacytoid morphology have fewer DNA breaks (Amaral et al., 2011), larger nucleolar sizes (Amaral, 2005), a high reactivity of Ki67 (MBI-1) (Gaspar, 2005), a higher proportion of metastases , and increased expression rates of p-glycoprotein (Gaspar et al., 2010). A direct consequence of this is the higher number of chemotherapy applications required to obtain initial regression (Gaspar et al., 2010). ...
The canine transmissible venereal tumour is a transplantable neoplasm of great scientific interest for its versatile biological behaviour and its complex mechanisms of evolution. The main objective of this research was to obtain information in order to carry out a better clinical and therapeutic approachof patients with this tumour, twenty dogs with clinical and cytological diagnosis of TVT were studied. Theclinical staging (TNM) was carried out, thecytomorphologicclassification and the nuclear malignancyand cytoplasmic criteria were obtained. TheChi-square test and the Mann- Whitney test were used for data analysis. Eighteen animals were mixed race with a 2 to 10 range of age, and the main location of the tumor was the external genital and the predominant cellular type was plasmacytoid. Themalignancynuclear and cytoplasmic criteria,with the exception of the perinuclear halo,were similar to those described in the literature. During the RNM classification, two tumours were categorized as T3M and one as T3N1; the other tumours were classified in different T degrees. Despite the lack of statistical significance for the employed method, in general, a good clinical relationship was seen between TNM staging and cytopathological findings, suggesting that both provide greater certainty about the degree of aggressiveness, progression and prognosis in the patients with TVT, as it occurs in other typesof tumours. Use of staging in this tumour can serve as a criterion to suggest the possible evolution and type of therapy.Nevertheless we recommend future research to help define the benefits of using the TNM clinical staging in TVT.
Canine transmissible venereal tumor (CTVT) is a contagious neoplasm, mainly transmitted through coitus. This round cell mesenchymal tumor is common in Brazil, often located in the genitalia although extragenital presentations may also occur, such as cutaneous, oral, and nasal forms. The objective of this study was to perform an epidemiological analysis of CTVT from published data in the recent academic literature to systematically demonstrate the distribution of CTVT in Brazil, identify the frequency of this neoplasm and its main diagnostic tests, and characterize its main clinical manifestations in Brazil. For such purpose, it was analyzed the scientific publications with cases of CTVT in Brazil, in English or Portuguese, published between 2000−2020. The CTVT was identified in 19 Brazilian states plus the Federal District, totaling 3,622 cases across the national territory, with the largest number of cases recorded in the Southeast region. The cytological exam was the most used for the diagnosis of CTVT (89.2 %), followed by histopathological (37.8 %) and immunohistochemistry (13.5 %)¹. Predominant epidemiological aspects of CTVT identified in the study were: Mixed breed dogs (75.2 %), females (62.5 %), in adulthood (between 2 and 7 years) and dogs with free extra outdoor access (91.1 %). Genital presentation was the most frequent in the literature (86 %), followed by cutaneous (21.8 %), nasal (10 %), oral and lymph nodes presentations (10−5 %) and less frequent manifestations as ocular and anal/perianal (< 5 %). CTVT is a neoplasm widely distributed in Brazil, highly frequent and with several forms of clinical presentation, which can be underdiagnosed if there is no adequate knowledge of this tumor and its epidemiological characteristics. The extragenital manifestations of the neoplasm need further studies for its better characterization and more precise definition of its frequencies.
TUMOR VENÉREO TRANSMISSÍVEL CANINO
RESUMO O tumor venéreo transmissível canino (TVTC) pode ser considerado uma das neoplasias mais comuns nesta espécie. Morfologicamente classificado como neoplasia de células redondas, acomete principalmente a mucosa genital externa de cães. A transmissão decorre da implantação de células tumorais durante o coito, brigas ou interações entre animais portadores e susceptíveis. Metástases raramente ocorrem. O diagnóstico é determinado pela história clínica, sinais clínicos e análise citológica e/ou histopatológica, e em alguns casos, a imuno-histoquímica pode ser necessária. O tratamento de escolha baseia-se na monoquimioterapia com sulfato de vincristina. Assim, objetivou-se por meio dessa revisão, reunir informações atualizadas sobre a origem desses tumores, bem como métodos de prevenção, diagnóstico e tratamento. Palavras-chave: cão, oncologia, resistência tumoral, TVT.
Canine transmissible venereal tumor
ABSTRACT: Canine transmissible venereal tumor (CTVT) is considered one of the most common neoplasms in dogs. Morphologically, it is classified as round cells tumor and it mainly affects the external genital mucosa of dogs. The transmission results from the implantation of tumor cells during intercourse, fights or interactions between susceptible animals. Metastases rarely occur. The diagnosis is based on clinical history, clinical signs and cytological and/or histopathology analysis, and in some cases, immunohistochemistry may be necessary. The first option of treatment is chemotherapy with vincristine sulfate. Thus, the purpose of this review was to gather updated information about the origin of these tumors and methods of prevention, diagnosis and treatment.
