35 results on '"Ctvt"'
Search Results
2. Origin, evolution, and global spread of a transmissible cancer clone
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Lawlor, Máire Julia and Murchison, Elizabeth
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Cancer ,Evolution ,Canine Transmissible Venereal Tumour ,Transmissible Cancer ,CTVT ,Canine Genetics ,Contagious Cancer ,Precontact Dogs ,Cancer Biology ,Mitochondrial Biology - Abstract
Clonally transmissible cancers are malignant cellular clones that spread between unrelated individuals by the physical transfer of living cancer cells. These clones can 'metastasise' through populations, having adapted to transmit across external environments and evade the host immune response. Canine Transmissible Venereal Tumour (CTVT) is a sexually transmitted genital tumour that affects dogs and has spread through dog populations worldwide. CTVT is the oldest known transmissible cancer and first arose thousands of years ago from the somatic cells of a single, 'founder' dog. The broad aim of this thesis was to advance understanding of biological features underlying CTVT's continued survival, as well as the evolutionary history that framed the origin of CTVT. In the first part of this thesis, I profile global tumour diversity using complete mitochondrial genome sequences (mtDNA) from 449 CTVT tumours collected from 39 countries in the first large-scale examination of CTVT clonal diversity. Phylogenetic characterisation of this clonal lineage showed that CTVT has captured mtDNA from transient hosts by horizontal transfer at least five times, defining distinct CTVT clades. Phylogeographic patterns and timings suggest the rapid, recent, multi-route dispersal of CTVT, likely via historic sea routes. Negative selection acts on tumour mtDNA to prevent the accumulation of deleterious mutations and there is evidence for multiple, complex mtDNA recombinations in CTVT. This is the first observed instance of mtDNA recombination in cancer. Enrichment of this data set with almost 200 additional mtDNAs uncovered further horizontal transfer and recombination events. These findings provide genetic evidence underpinning the importance of functional mitochondria in CTVT evolution. In the second part of this thesis, by analysing genomic data from ancient and modern canids alongside CTVT whole genomes, I describe the ancestry of the CTVT founder and the likely spatiotemporal origin of the disease. The CTVT progenitor belonged to a monophyletic lineage of high-latitude dogs that likely originated in North East Asia and dispersed into the Americas alongside people. Using a pair of CTVT biopsies derived from a naturally occurring direct transmission with a known transmission time interval, I estimated the somatic mutation rate in CTVT and inferred the time of CTVT origin. Finally, I make a case for systematically screening cancers with high prevalence in wildlife species for a transmissible cancer etiology. This work traces the emergence of CTVT, along with detailed geographical and temporal routes of transmissible cancer disease spread over the past two thousand years, and offers new perspectives on the history of dogs as well as key insights into biological mechanisms driving the hitchhiking cancer that has accompanied them around the world.
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- 2019
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3. Genome diversity and evolution in canine transmissible venereal tumour
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Strakova, Andrea and Murchison, Elizabeth P.
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636.7 ,canine transmissible venereal tumour ,cancer ,veterinary ,transmissible cancer ,canine ,dog ,genetics ,DNA sequencing ,evolution ,CTVT ,worldwide distribution ,histology ,mitochondrial genome ,contagious cancer ,CTVT distribution and prevalence ,historical spread ,genetic diversity ,phenotypic diversity - Abstract
The canine transmissible venereal tumour (CTVT) is a contagious cancer that is naturally transmitted between dogs by the allogeneic transfer of living cancer cells during coitus. CTVT first arose several thousand years ago and has been reported in dog populations worldwide. The goals of this Thesis were (1) to gain further understanding of CTVT distribution patterns and prevalence around the world, (2) to use genetics to trace the historical spread of CTVT and (3) to map the genetic as well as phenotypic diversity of CTVT tumours around the world. To understand the distribution patterns of CTVT, I obtained information from 645 veterinarians and animal health workers in 109 countries, and generated a snapshot of the locations in which this disease is found. Additionally, as preparation for further genetic analysis, I collected samples from over one thousand CTVT cases from more than 50 countries, optimised methods for high-throughput DNA extraction and quantification and optimised a qPCR-based assay for CTVT diagnosis and host contamination detection. With the goal of tracing the historical spread of CTVT and learning about the genetic diversity of this disease, I sequenced complete mitochondrial genomes of 449 CTVT tumours and their matched hosts. The analysis of the CTVT mitochondrial diversity revealed that CTVT has captured mitochondrial DNA (mtDNA) through horizontal transfer events at least five times during the history of the lineage, delineating five tumour clades. CTVT appears to have spread rapidly around the world within the last 2,000 years, perhaps transported by dogs travelling along historic maritime trade routes. This work indicated that negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and that recombination has caused occasional mtDNA re-assortment. A histology-based screen of CTVT clades did not show any significant phenotypic differences between groups. In order to determine how the five mtDNA clades relate to each other, I analysed data from 539 CTVT exomes. This revealed that a single canine mtDNA haplogroup has recurrently and recently undergone multiple horizontal transfer events. Analysis of this haplotype highlighted a number of candidate genetic variants which may be conferring a selective advantage to this haplotype in CTVT, possibly by influencing mtDNA transcription or replication. Overall, genetic and phenotypic analysis of CTVT tumours from across the globe has broadened our understanding of CTVT diversity, and provided important insights into the biology of a unique transmissible cancer.
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- 2018
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4. Canine Populations in Vicinity are Propagating Canine Transmissible Venereal Tumour in Pakistan - A Pilot Study.
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Awan, Furqan, Nawaz, Sadia, Ali, Muhammad Muddassir, Iqbal, Asia, Akhtar, Raheela, Firyal, Sehrish, Sadia, Haleema, Javid, Arshad, Rashid, Muhammad, Taseer, Muhammad Sulman Ali, and Zhenling Zeng
- Abstract
The aim of this study was to record the distribution and the spatial and temporal trends of canine transmissible venereal tumor (CTVT) in pet dogs; and identify the potential factors that are playing important role in disease spread. A questionnaire-based study was conducted to identify the conditions and circumstances of CTVT affected dogs that presented to veterinary practices over a 12-month period. The practices were conveniencesampled on the basis of voluntary participation. Forty practices were approached, and veterinarians from 24 practices agreed to participate. Data were provided on 96 original presentations, excluding revisits, of which 47.92% were intact males and 52.08% were intact females with the mean age of 3.98 years. Moreover, further 96 controls were selected from the same clinical practices with same parameters. Among the dogs meant for different purposes, guarding purpose dogs were found more affected (n=59). While among the dog breeds, Labrador were over-represented (n=26) followed by mongrel dogs (bully, n=23). In winter season, higher number of cases (n=34; from November to February) was recorded as compared to other seasons. To explore further important features, non-linear categorical PCA was employed. Prominently canine populations in the vicinity were found to be more varied. This is the first epidemiological study done in Pakistan that has identified some novel trends and circumstances regarding the CTVT. [ABSTRACT FROM AUTHOR]
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- 2022
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5. CYTOLOGICAL DIAGNOSIS AND THERAPEUTIC MANAGEMENT OF CANINE TRANSMISSIBLE VENEREAL TUMOR (CTVT) - A CASE REPORT.
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Devi, N. Bhumapati, Laltlankimi, Ozukum, Sashitola, Kuotsu, Keneisezo, Kuotsu, Neithono, Das, Gunjan, Devi, K. Merina, Devi, T. Gyaneshori, Chutia, Tukheswar, and Jayathangaraj, M. G.
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TRANSMISSIBLE tumors , *AGRICULTURE , *ANIMAL culture , *VETERINARY medicine , *DIAGNOSIS - Abstract
A two years old non-descript bitch was presented to the Veterinary Clinical Complex, College of Veterinary Sciences and Animal Husbandry, Central Agricultural University, Jalukie, Nagaland with the history that the bitch was mated couple of days back and after bleeding was seen from the vagina for the last two weeks. Anamnestic data revealed normal rectal temperature of 102 °F. Upon clinical examination, it was found that there was a multilobular typical cauliflower shaped tumerous like growth projecting from the vulva. Impression smear of tumour cell was prepared and was observed under oil immersion microscope. Cytological evaluation showed high cellularity and presence of large number of pleomorphic cells, anisokaryosis with multiple nucleoli and coarse chromatin, light basophilic cytoplasm and abundant number of vacuolated cytoplasm, all conclusive of cytological diagnosis of CTVT. Chemotherapy with vincristine sulfate @ 0.025 mg/kg BW was administered weekly for 4 weeks and found that the tumour mass subsided without any complaint of further reoccurrence. [ABSTRACT FROM AUTHOR]
- Published
- 2022
6. In vitro Effect of Recombinant Feline Interferon-Ω (rFeIFN-Ω) on the Primary CanineTransmissible Venereal Tumor Culture
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Chanokchon Setthawongsin, Sirikachorn Tangkawattana, Anudep Rungsipipat, and Somporn Techangamsuwan
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CTVT ,interferon ,in vitro study ,primary culture ,rFeIFN-Ω ,Veterinary medicine ,SF600-1100 - Abstract
Background: Interferons (IFNs), signaling proteins produced by host cells, are secreted in response to pathogen activity as well as to tumor cells, and display antiviral, antiproliferative, and immunomodulatory effects. Recombinant feline interferon omega (rFeIFN-ω) has in vitro growth inhibition activities on various canine and feline tumor cell lines. Canine transmissible venereal tumor (CTVT) is used as an animal model for immunotherapy due to its specific growth phase. Previous studies have usually focused on the interaction between tumor infiltrating lymphocytes (TILs) and CTVT cells. However, the specific effects of rFeIFN-ω on CTVT cells remains poorly defined.Aims: The aims of this study, therefore, were to evaluate the in vitro effect of rFeIFN-ω on primary CTVT cells and to study the mRNA expression of apoptotic genes and drug resistance genes.Materials and Methods: Purified CTVT cells were treated with various concentrations of rFeIFN-ω and the viability of the cultured cells was ascertained at 24, 48, and 72 h post treatment (hpt) and a dose-response curve plotted. The mRNA expression of apoptotic (BAX and BCL-2) and drug resistance (ABCB1 and ABCG2) genes was performed by reverse transcription quantitative real-time PCR at 72 hpt.Results: rFeIFN-ω displayed an effect against CTVT cell viability, which decreasing viability in a dose-dependent manner within 72 hpt. The relative mRNA expression of BCL-2 was upregulated only at a rFeIFN-ω concentration of 104 IU/100 μl. However, higher concentrations of rFeIFN-ω gave a higher level of relative mRNA expression of ABCB1 transporter gene.Conclusion: This study provided the information of in vitro effect of rFeIFN-ω on CTVT cell viability in a dose dependent manner, as well as, the alteration of BCL-2 and ABCB1 gene expression after treatment. These results encourage future in vivo studies to evaluate the potential efficacy of this treatment in CTVT cases.
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- 2019
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7. Prevalence of different cytomorphological types of transmissible venereal tumours and the association with prognosis in dogs treated with vincristine sulphate – Retrospective study
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Cristiane Sella Paranzini, Marcos César Sant’anna, Giovana Wingeter di Santis, and Maria Isabel Mello Martins
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CTVT ,Cytology ,Prognosis. ,Agriculture (General) ,S1-972 - Abstract
Canine transmissible venereal tumours (CTVT) are the most commonly diagnosed tumours in veterinary hospitals. CTVT is morphologically classified as a round cell tumour, although the exact origin of the cells is unknown. Immunohistochemical studies have suggested histiocytic and mesenchymal origin. CTVT can be classified as lymphocyte-like, plasmocyte-like, and mixed according to their cytomorphological features. The treatment of choice for CTVT is chemotherapy with vincristine sulphate applied weekly; this produces a good prognosis. However, an increase in the number of chemotherapy applications and adjuvant therapies has become common. The aim of this study was to determine the association of cytomorphological types of CTVT with resistance and partial resistance to vincristine sulphate and the possible need for a large number of chemotherapy sessions. A retrospective study of a 24-month period evaluated 46 diagnosed and treated cases of CTVT. It was concluded that there is a higher prevalence of plasmacyte-like, followed by mixed and lymphocyte-like CTVT. The cytomorphological type did not differ in relation to the response to the treatments with vincristine sulphate and the number of chemotherapy sessions necessary for CTVT regression has increased by factors not yet elucidated.
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- 2015
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8. Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs?
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Ballestero Fêo, H., Montoya Flórez, L., Yamatogi, R. S., Prado Duzanski, A., Araújo, J. P., Oliveira, R. A., and Rocha, N. S.
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CANCER in dogs , *TRANSMISSIBLE tumors , *NEOPLASTIC cell transformation , *THERAPEUTIC use of interferons , *DIAGNOSIS ,IMMUNE system physiology - Abstract
The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread naturally between dogs, with the ability to develop and evade the immune system, despite strict immune surveillance of the host. Furthermore, molecular signalling between cells of the immune system and the tumour microenvironment appear to influence the behaviour and development of the tumour. Thus, this study aimed to quantify the expression of genes related to the immune system such as IL‐6, IFN‐γ, and TGF‐β, as well as angiogenic factors (VEGF, CXCR4), in CTVT cells in vivo and in vitro (primary culture), correlating with the clinical response of the animals treated with vincristine. As expected, the most prevalent subtype was plasmacytoid cells, although lymphocytic cells were also found, indicating the possibility of polyclonality. When we compared the gene expressions of IFN‐γ and IL‐6, we mostly found low expression, concluding that MHC expression was probably not occurring in tumour cells, and no activation of immune cells to eliminate the tumour. The TGF‐β gene was normal in the majority of animals but demonstrated decreased expression in vincristine resistant animals, leading to the hypothesis that the concentration of tumour‐derived TGF‐β was affecting and even suppressing the real TGF‐β expression, favouring tumour proliferation and progression in these cases. VEGF expression was extremely high, demonstrating its angiogenic role in tumour growth, while CXCR4 was decreased, possibly because of CTVT’s low metastatic potential. Thus, we concluded that the tumour microenvironment, together with the immune system of the host, influences CTVT, presumably altering its tumorigenesis and the animal’s clinical response to treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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9. Computer tomographic imaging in 4 dogs with primary nasal canine transmissible venereal tumor and differing cellular phenotype.
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Ojeda, Javier, Mieres, Marcelo, Soto, Francisco, Arnes, Verónica, Paredes, Enrique, and Navarrete, María
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DOG diseases , *PHENOTYPES , *COMPUTED tomography , *TUMOR diagnosis , *CANCER chemotherapy - Abstract
Primary nasal canine transmissible venereal tumor (CTVT) without genital affection is uncommon. The aim of this report was to describe the primary nasal CTVT findings and CT staging in 4 dogs with different cytological phenotypes. Three male dogs and 1 bitch were evaluated for their chronic histories of sneezing, snoring, mucopurulent nasal discharge and nasal deformation. Cytological examination of nasal secretions suggested CTVT, confirmed by histopathological examination and LINE-1/c-myc. Males had the plasmacytoid phenotype of CTVT, and the bitch had the lymphocytoid phenotype. CTVT were staged based on the CT findings using modified Adams staging system. The bitch was classified as stage 1, 2 males were classified as stage 3 and 1 male as stage 4. All dogs had a complete tumoral remission after chemotherapy. Plasmacytoid phenotype was identified in cases with most important damage of the nasal cavity. However, the cytological type did not affect the response to chemotherapy. [ABSTRACT FROM AUTHOR]
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- 2018
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10. Identification of mitochondrial DNA transfer in canine transmissible venereal tumours obtained from dogs in Mexico.
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Bautista-Gómez, Linda and Martínez-Castañeda, Simón
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MITOCHONDRIAL DNA , *CELL transplantation , *TUMORS , *DOG genetics , *TRANSMISSIBLE tumors , *DOG diseases , *TUMORS in animals , *GENETICS , *CANCER , *MAMMALS ,TRANSMISSION - Abstract
Canine transmissible venereal tumour (CTVT) has been transmitted by cell transplantation from dog to dog, for over 10 000 years. Although initial studies report a single genetic origin for CTVT, recent samples from around the world reveal high genetic diversity. An elevated number of polymorphisms have been determined in mitochondrial DNA (mtDNA) of CTVT. The recent discovery of mtDNA transference from the host into tumoural cells could be a novel source of genetic diversity in CTVT. The aim of this study was to determine the presence of host mtDNA in samples of CTVT in Mexican dogs. Genotyping of 49 samples of CTVT and 49 samples of blood cells pertaining to affected dogs was performed by direct sequencing from the mtDNA D-loop region. Exogenous mtDNA was observed in 6% of the analysed tumours. This is the first investigation reporting the prevalence of exogenous mtDNA in CTVT in the Mexican dog population. [ABSTRACT FROM PUBLISHER]
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- 2017
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11. Immunohistochemical, lectin histochemical and ultrastructural studies of canine transmissible venereal tumor in Brazil.
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Mascarenhas, Mariana B., Peixoto, Paulo V., Ramadinha, Regina R., Armien, Anibal G., Costa, Samay Z., Miranda, Ileana C., Nogueira, Vivian A., and França, Ticiana N.
- Abstract
Copyright of Pesquisa Veterinaria Brasileira is the property of Colegio Brasileiro de Patologia Animal - CBPA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2017
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12. Could dysregulation of RASSF1 expression be a mechanism of tumorigenesis in CTVT?
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Haline B. Fêo, Luis Mauricio M. Flórez, Ricardo S. Yamatogi, Anderson P. Duzanski, João P. Araújo Junior, Rogerio A. Oliveira, and Noeme S. Rocha
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Dysregulation ,tumorigenesis ,General Veterinary ,canine transmissible venereal tumor ,CTVT ,RASSF1 - Abstract
Canine transmissible venereal tumor (CTVT) is the oldest known somatic cell lineage. It is a transmissible cancer that propagates naturally in dogs and reportedly contains gene mutations. RASSF1 participates in DNA damage repair, and its downregulation, results in tumor progression. Hence, RASSF1 is a tumor suppressor gene. Its expression was quantified in tumors from seventeen animals and three cell cultures derived from tumors. In general, RASSF1 was underexpressed in 65%, and absent in 35% of tumor samples. Cells from tumor tissue cultures showed decreased expression of RASSF1 in 67% and elevated expression in 33% of samples tested. The tumor tissues showed significantly lower levels of RASSF1 expression compared to cultured cells. Previously we reported that both the tumor microenvironment and the host immune system appear to influence the tumorigenesis and stage of CTVT. This is the first article to demonstrate the expression of RASSF1 in CTVT. Decreased RASSF1 possibly helps tumor progression.
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- 2022
13. Fibrosis in canine transmissible venereal tumor after chemotherapy with vincristine.
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Duzanski ADP, Feo HB, Montoya Flórez LM, Dinau FC, Paiva BR, Brandão CVS, and Rocha NS
- Abstract
The canine transmissible venereal tumor is type of transmissible cancer that occurs naturally through allogenic cellular transplants. Commonly diagnosed in the genital area of sexually active dogs, the tumor typically responds well to vincristine sulfate chemotherapy, although there are cases of resistance to the drug correlated with the tumoral phenotype. We describe herein a case of fibrosis in an area affected by the tumor in a dog after vincristine chemotherapeutic treatment that was associated with an idiosyncratic reaction to the drug., Competing Interests: Conflict of interests: The authors declared that there are no potential conflicts of interest with respect to the authorship and/or publication of this article.
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- 2023
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14. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis.
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SETTHAWONGSIN, Chanokchon, TECHANGAMSUWAN, Somporn, TANGKAWATTANA, Sirikachorn, and RUNGSIPIPAT, Anudep
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POLYMERASE chain reaction ,CANINE parvovirus ,CYTOLOGICAL techniques - Abstract
Canine transmissible venereal tumor (CTVT) is the only naturally contagious tumor that is transmitted during coitus or social behaviors. Based on the tumor's location, the diagnosis of genital TVT (GTVT) is comparably easier than those in the extragenital area (ETVT) that are more easily incorrectly diagnosed. Fortunately, CTVT cells contain a specific long interspersed nuclear elements (LINE), inserted upstream of the myc gene, allowing a diagnostic polymerase chain reaction (PCR) based detection assay. The objectives of this study were aimed to improve the diagnostic accuracy by applying the diagnostic LINE1-c-myc PCR assay and fine needle aspiration (FNA) collection in direct comparison with standard cytological and histopathological analyses. Seventy-four dogs, comprised of 41 and 31 dogs with tumor masses at their external genitalia and extragenital areas (e.g. skin and nasal cavity), respectively, were included in this study. The signalment of these 65 dogs and clinical history of 20 client-owned dogs were collected. Samples were taken by biopsy for both histopathological examination and FNA for cytological examination and diagnostic PCR. The PCR products from 10 apparently CTVT samples were purified and sequenced. Sixty-one CTVT cases were diagnosed by cytological and histological analyses, but 65 were positive by the PCR assay. Overall, the PCR assay improved the accuracy of diagnostic CTVT results, especially for the more difficult ETVT tumors. Moreover, this PCR-based approach can facilitate the decision as to discontinue chemotherapy by discrimination between residual tumor cell masses and fibrotic tissue. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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15. Cell-mediated immunity and expression of MHC class I and class II molecules in dogs naturally infected by canine transmissible venereal tumor: Is there complete spontaneous regression outside the experimental CTVT?
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Anderson do Prado Duzanski, Luis Mauricio Montoya Flórez, Haline Ballestero Fêo, Graziela Gorete Romagnoli, Ramon Kaneno, Noeme Sousa Rocha, Universidade Estadual Paulista (UNESP), and COL Veterinary Pathology Research Group
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Immunity, Cellular ,General Veterinary ,Macrophages ,CTVT ,Flow Cytometry ,Regression ,Dogs ,Tumor immunity ,Dog ,Chemotherapy ,Animals ,Flow cytometry ,Dog Diseases ,Venereal Tumors, Veterinary - Abstract
Made available in DSpace on 2022-04-29T08:40:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-07-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The canine transmissible venereal tumor (CTVT) is a transplantable cancer with the ability evade the immune system, despite strict immune surveillance of the host; in this context, the relationship between inflammatory infiltrate and CTVT prognosis is not entirely understood. Natural canine transmissible venereal tumors of 22 dogs were evaluated for tumor/host interaction through clinical and epidemiological data, cyto-histopathological and cytogenetic findings and, mainly, cell-mediated immune response. We performed analysis on dogs with naturally acquired disease to provide information from the study of CTVT biology in its natural course, as the clinical evolution of the natural tumor in the host is not yet as well known as in the laboratory. Populations for T cell labeling (CD3+ CD4+ CD8+), B cells, NK cells, and macrophages were analyzed by flow cytometry in blood and tumor samples and expressions of MHC class I and class II molecules were quantified by immunohistochemistry and compared mainly between the phases of progression and regression in the natural CTVT. Dogs were also treated with vincristine sulfate and evaluated for chemotherapeutic response. Chemotherapy was effective in 88% of cases and there was no recurrence of the disease 12 months after the cure. Tumor cells displayed a numerical chromosomal variation between 54 and 72, not correlating with the host genotype. Although a greater expression of MHC molecules [18.6 ± 5.8% class I (P < 0.004) and 38.5 ± 6.5% class II (P < 0.003)] was observed in the regression phase, no significant effect was observed between the clinical phase of the tumor and cellular immune response in the analysis by flow cytometry (P > 0.05). We also found no correlation between cytological subtype of the tumor (plasmacytoid, lymphocytoid and mixed) and cellular immune response, suggesting that there is no difference in tumor immunogenicity. Here, we found no immunological evidence to support the theory of the immune-induced complete spontaneous regression in CTVT. Department of Pathology Botucatu Medical School (FMB) State University of São Paulo (UNESP), SP Laboratory of investigative and Comparative Pathology School of Veterinary Medicine and Animal Sciences (FMVZ) State University of São Paulo (UNESP), SP Faculty of Veterinary Medicine Universidad Nacional de Colombia COL Veterinary Pathology Research Group Laboratory of tumor immunology Institute of Biosciences of Botucatu (IBB) State University of São Paulo (UNESP), SP Department of Pathology Botucatu Medical School (FMB) State University of São Paulo (UNESP), SP Laboratory of investigative and Comparative Pathology School of Veterinary Medicine and Animal Sciences (FMVZ) State University of São Paulo (UNESP), SP Laboratory of tumor immunology Institute of Biosciences of Botucatu (IBB) State University of São Paulo (UNESP), SP CNPq: CNPq 445250/2014-3
- Published
- 2021
16. Gene-expression profiling to identify genes related to spontaneous tumor regression in a canine cancer model
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Chiang, Hsin-Chien, Liao, Albert Tai-Ching, Jan, Tong-Rong, Wang, Yu-Shan, Lei, Han-Jung, Tsai, Mong-Hsun, Chen, Mo-Fen, Lee, Chien-Yueh, Lin, Yi-Chen, Chu, Rea-Min, and Lin, Chen-Si
- Subjects
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GENE expression , *SPONTANEOUS cancer regression , *ANIMAL models in research , *MICROARRAY technology , *DOGS , *CANCER in animals , *IMMUNE response - Abstract
Abstract: Microarray transcriptome study in cancer has been commonly used to investigate tumorigenic mechanisms. The unique growth pattern of spontaneous regression (SR) after progressive (P) growth in canine transmissible venereal tumor (CTVT) provides a valuable cancer model to study the genome-wide differences in samples between the two stages of growth. In this study, Affymetrix analysis was performed based on the canine genome to compare the gene expression profiles of CTVT P- and SR-phase tumors. A total of 459 (278 up-regulated and 181 down-regulated) genes were identified as being differentially-expressed during the SR phase by the 2-fold method. Further analysis of these genes revealed that the expression of three genes associated with IL-6 production –TIMD-4, GPNMB and PLTP – was significantly higher in SR-phase tumors than in P-phase tumors; these results were also confirmed by real time RT-PCR in tumor tissues of beagles. In addition, we found that Th17-related genes were over-expressed in the SR phase, suggesting autoimmune responses involvement in tumor regression. Although the interaction between CTVT and host immunity were partially investigated in previous studies, our results enable us to gain new insight into the genes and possible mechanisms involved in tumor regression and reveal potentially useful targets for cancer therapy. [Copyright &y& Elsevier]
- Published
- 2013
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17. Cell-mediated immunity and expression of MHC class I and class II molecules in dogs naturally infected by canine transmissible venereal tumor: Is there complete spontaneous regression outside the experimental CTVT?
- Author
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do Prado Duzanski A, Flórez LMM, Fêo HB, Romagnoli GG, Kaneno R, and Rocha NS
- Subjects
- Animals, Dogs, Flow Cytometry veterinary, Immunity, Cellular, Macrophages, Dog Diseases genetics, Venereal Tumors, Veterinary pathology
- Abstract
The canine transmissible venereal tumor (CTVT) is a transplantable cancer with the ability evade the immune system, despite strict immune surveillance of the host; in this context, the relationship between inflammatory infiltrate and CTVT prognosis is not entirely understood. Natural canine transmissible venereal tumors of 22 dogs were evaluated for tumor/host interaction through clinical and epidemiological data, cyto-histopathological and cytogenetic findings and, mainly, cell-mediated immune response. We performed analysis on dogs with naturally acquired disease to provide information from the study of CTVT biology in its natural course, as the clinical evolution of the natural tumor in the host is not yet as well known as in the laboratory. Populations for T cell labeling (CD3
+ CD4+ CD8+ ), B cells, NK cells, and macrophages were analyzed by flow cytometry in blood and tumor samples and expressions of MHC class I and class II molecules were quantified by immunohistochemistry and compared mainly between the phases of progression and regression in the natural CTVT. Dogs were also treated with vincristine sulfate and evaluated for chemotherapeutic response. Chemotherapy was effective in 88% of cases and there was no recurrence of the disease 12 months after the cure. Tumor cells displayed a numerical chromosomal variation between 54 and 72, not correlating with the host genotype. Although a greater expression of MHC molecules [18.6 ± 5.8% class I (P < 0.004) and 38.5 ± 6.5% class II (P < 0.003)] was observed in the regression phase, no significant effect was observed between the clinical phase of the tumor and cellular immune response in the analysis by flow cytometry (P > 0.05). We also found no correlation between cytological subtype of the tumor (plasmacytoid, lymphocytoid and mixed) and cellular immune response, suggesting that there is no difference in tumor immunogenicity. Here, we found no immunological evidence to support the theory of the immune-induced complete spontaneous regression in CTVT., (Copyright © 2022. Published by Elsevier Ltd.)- Published
- 2022
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18. Overexpression of chemokine ligand 7 is associated with the progression of canine transmissible venereal tumor.
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Hsin-Chien Chiang, Yu-Shan Wang, Chung-Hsi Chou, Taiching Liao, Albert, Rea-Min Chu, and Chen-Si Lin
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CHEMOKINES , *TUMOR growth , *MESSENGER RNA , *LEUCOCYTES , *TRANSFORMING growth factors - Abstract
Background: Chemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-β derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-β in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT). Results: We have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1β and TGF-β had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression. Conclusion: CXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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19. Analysis of canine transmissible veneral tumor genotypes using the D-loop region of mitochondrial DNA.
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Bautista.-Gómez, Linda G., Martínez.-Castañeda, Simón, Córdova.-Alarcón, Emilio, and Vázquez.-Chagoyán, Juan Carlos
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MITOCHONDRIAL DNA ,HAPLOTYPES ,CELL transformation ,BLOOD sampling ,PARSIMONIOUS models - Abstract
Canine transmissible venereal tumor (CTVT) is the only neoplasm that can be spread among dogs through cell transplantation. Therefore, this tumor does not originate from host cell transformation. Although CTVT has a monophyletic origin, several studies have shown the presence of genetic diversity which was probably acquired after the development of its original clone. To investigate the genetic diversity of CTVT in Mexico and its relation with CTVTs disseminated worldwide, we sequenced a fragment of mitochondrial DNA in 50 tumor samples and matched blood samples from dog hosts from Mexico. We found ten new haplotypes in tumor samples, which were all distinct from their matched host. The TVT1 haplotype was the most frequent in our samples, suggesting that it could be the origin of the others. We found that haplotypes in Mexico and other countries are distributed in two well-defined clusters. Our data also suggest a close relationship among American haplotypes (Mexico, USA, Chile and Brazil). Interestingly, these American haplotypes were also closely related to Asian haplotypes. Taking into account the estimated timing of the origin of CTVT, we propose that CTVT might have originated in Asia; consequently, haplotypes currently present in America could descend from Asiatic lineages. [ABSTRACT FROM AUTHOR]
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- 2011
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20. Chicken HSP70 DNA vaccine inhibits tumor growth in a canine cancer model
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Yu, Wen-Ying, Chuang, Tien-Fu, Guichard, Cécile, El-Garch, Hanane, Tierny, Dominique, Laio, Albert Taiching, Lin, Ching-Si, Chiou, Kuo-Hao, Tsai, Cheng-Long, Liu, Chen-Hsuan, Li, Wen-Chiuan, Fischer, Laurent, and Chu, Rea-Min
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- *
DNA vaccines , *HEAT shock proteins , *TUMOR growth , *CANCER treatment , *ANTIGENS , *CANCER invasiveness , *DRUG efficacy , *LABORATORY dogs - Abstract
Abstract: Immunization with xenogeneic DNA is a promising cancer treatment to overcome tolerance to self-antigens. Heat shock protein 70 (HSP70) is over-expressed in various kinds of tumors and is believed to be involved in tumor progression. This study tested a xenogeneic chicken HSP70 (chHSP70) DNA vaccine in an experimental canine transmissible venereal tumor (CTVT) model. Three vaccination strategies were compared: the first (PE) was designed to evaluate the prophylactic efficacy of chHSP70 DNA vaccination by delivering the vaccine before tumor inoculation in a prime boost setting, the second (T) was designed to evaluate the therapeutic efficacy of the same prime boost vaccine by vaccinating the dogs after tumor inoculation; the third (PT) was similar to the first strategy (PE), with the exception that the electroporation booster injection was replaced with a transdermal needle-free injection. Tumor growth was notably inhibited only in the PE dogs, in which the vaccination program triggered tumor regression significantly sooner than in control dogs (NT). The CD4+ subpopulation of tumor-infiltrating lymphocytes and canine HSP70 (caHSP70)-specific IFN-γ-secreting lymphocytes were significantly increased during tumor regression in the PE dogs as compared to control dogs, demonstrating that specific tolerance to caHSP70 has been overcome. In contrast, no benefit of the therapeutic strategy (T) could be noticed and the (PT) strategy only led to partial control of tumor growth. In summary, antitumor prophylactic activity was demonstrated using the chHSP70 DNA vaccine including a boost via electroporation. Our data stressed the importance of DNA electroporation as a booster to get the full benefit of DNA vaccination but also of cancer immunotherapy initiation as early as possible. Xenogeneic chHSP70 DNA vaccination including an electroporation boost is a potential vaccine to HSP70-expressing tumors, although further research is still required to better understand true clinical potential. [Copyright &y& Elsevier]
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- 2011
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21. Clonally transmissible cancers in dogs and Tasmanian devils.
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Murchison, E. P.
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CANCER , *INFECTIOUS disease transmission , *HOMOGRAFTS , *DOG diseases , *TASMANIAN devil , *ETIOLOGY of diseases , *DISEASES - Abstract
Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are the only known naturally occurring clonally transmissible cancers. These cancers are transmitted by the physical transfer of viable tumor cells that can be transplanted across histocompatibility barriers into unrelated hosts. Despite their common etiology, DFTD and CTVT have evolved independently and have unique life histories and host adaptations. DFTD is a recently emerged aggressive facial tumor that is threatening the Tasmanian devil with extinction. CTVT is a sexually transmitted tumor of dogs that has a worldwide distribution and that probably arose thousands of years ago. By contrasting the biology, molecular genetics and immunology of these two unusual cancers, I highlight the common and unique features of clonally transmissible cancers, and discuss the implications of clonally transmissible cancers for host-pathogen evolution. [ABSTRACT FROM AUTHOR]
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- 2008
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22. Canine transmissible venereal tumor cell depletion of B lymphocytes: molecule(s) specifically toxic for B cells
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Liao, Kuang-Wen, Hung, Shao-Wen, Hsiao, Ya-Wen, Bennett, Michael, and Chu, Rea-Min
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- *
B cell lymphoma , *SEXUALLY transmitted diseases , *TUMOR growth - Abstract
Canine transmissible venereal tumor (CTVT) is an excellent model for investigating the interaction between host immunity and tumor growth. Although CTVT is an allograft, initially the host immune system is unable to destroy the tumor cells, and the tumor grows progressively for about 4–6 months (P phase). After a short stable phase, the tumor undergoes regression (R phase). In this study, CTVT inoculation significantly reduced the proportion of B lymphocytes among all peripheral blood lymphocytes (PBL), but the proportion of B lymphocytes returned to normal after complete removal of CTVT. Following CTVT inoculation, immunoglobulin concentrations decreased gradually, coincident with B lymphocyte decline. Furthermore, CTVT secreted a soluble, heat- and protease K-sensitive cytotoxic molecule(s) that destroyed peripheral blood B lymphocytes (PBBL) but spared other types of immune cells regardless of whether mitogens, such as IL-2 or Con A, were present. The decrease in the proportion and viability of PBBL was caused by a cytotoxic molecule(s) that induced apoptosis. The molecular weight of the CTVT-derived cytotoxic molecule(s) was 30–100 kDa. Human, domestic cat, horse and mouse B cells were also sensitive to the substance. [Copyright &y& Elsevier]
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- 2003
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23. In vitro Effect of Recombinant Feline Interferon-Ω (rFeIFN-Ω) on the Primary CanineTransmissible Venereal Tumor Culture
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Somporn Techangamsuwan, Chanokchon Setthawongsin, Anudep Rungsipipat, and Sirikachorn Tangkawattana
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in vitro study ,040301 veterinary sciences ,medicine.medical_treatment ,CTVT ,Biology ,Canine transmissible venereal tumor ,0403 veterinary science ,03 medical and health sciences ,Interferon ,In vivo ,medicine ,Viability assay ,030304 developmental biology ,Original Research ,0303 health sciences ,primary culture ,lcsh:Veterinary medicine ,General Veterinary ,Tumor-infiltrating lymphocytes ,04 agricultural and veterinary sciences ,Immunotherapy ,interferon ,medicine.disease ,In vitro ,rFeIFN-Ω ,Apoptosis ,Cancer research ,lcsh:SF600-1100 ,Veterinary Science ,medicine.drug - Abstract
Background: Interferons (IFNs), signaling proteins produced by host cells, are secreted in response to pathogen activity as well as to tumor cells, and display antiviral, antiproliferative, and immunomodulatory effects. Recombinant feline interferon omega (rFeIFN-ω) has in vitro growth inhibition activities on various canine and feline tumor cell lines. Canine transmissible venereal tumor (CTVT) is used as an animal model for immunotherapy due to its specific growth phase. Previous studies have usually focused on the interaction between tumor infiltrating lymphocytes (TILs) and CTVT cells. However, the specific effects of rFeIFN-ω on CTVT cells remains poorly defined. Aims: The aims of this study, therefore, were to evaluate the in vitro effect of rFeIFN-ω on primary CTVT cells and to study the mRNA expression of apoptotic genes and drug resistance genes. Materials and Methods: Purified CTVT cells were treated with various concentrations of rFeIFN-ω and the viability of the cultured cells was ascertained at 24, 48, and 72 h post treatment (hpt) and a dose-response curve plotted. The mRNA expression of apoptotic (BAX and BCL-2) and drug resistance (ABCB1 and ABCG2) genes was performed by reverse transcription quantitative real-time PCR at 72 hpt. Results: rFeIFN-ω displayed an effect against CTVT cell viability, which decreasing viability in a dose-dependent manner within 72 hpt. The relative mRNA expression of BCL-2 was upregulated only at a rFeIFN-ω concentration of 104 IU/100 μl. However, higher concentrations of rFeIFN-ω gave a higher level of relative mRNA expression of ABCB1 transporter gene. Conclusion: This study provided the information of in vitro effect of rFeIFN-ω on CTVT cell viability in a dose dependent manner, as well as, the alteration of BCL-2 and ABCB1 gene expression after treatment. These results encourage future in vivo studies to evaluate the potential efficacy of this treatment in CTVT cases.
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- 2019
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24. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis
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Anudep Rungsipipat, Sirikachorn Tangkawattana, Chanokchon Setthawongsin, and Somporn Techangamsuwan
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0301 basic medicine ,Nasal cavity ,Male ,Pathology ,medicine.medical_specialty ,040301 veterinary sciences ,diagnosis ,Veterinary pathology ,Genes, myc ,LINE ,CTVT ,Canine transmissible venereal tumor ,Polymerase Chain Reaction ,law.invention ,0403 veterinary science ,03 medical and health sciences ,Dogs ,law ,Biopsy ,medicine ,Neoplasm ,Animals ,Dog Diseases ,Polymerase chain reaction ,Venereal Tumors, Veterinary ,Gene Rearrangement ,General Veterinary ,medicine.diagnostic_test ,Full Paper ,business.industry ,04 agricultural and veterinary sciences ,Gene rearrangement ,DNA, Neoplasm ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Fine-needle aspiration ,PCR ,Long Interspersed Nucleotide Elements ,FNA ,Female ,business - Abstract
Canine transmissible venereal tumor (CTVT) is the only naturally contagious tumor that is transmitted during coitus or social behaviors. Based on the tumor's location, the diagnosis of genital TVT (GTVT) is comparably easier than those in the extragenital area (ETVT) that are more easily incorrectly diagnosed. Fortunately, CTVT cells contain a specific long interspersed nuclear elements (LINE), inserted upstream of the myc gene, allowing a diagnostic polymerase chain reaction (PCR) based detection assay. The objectives of this study were aimed to improve the diagnostic accuracy by applying the diagnostic LINE1-c-myc PCR assay and fine needle aspiration (FNA) collection in direct comparison with standard cytological and histopathological analyses. Seventy-four dogs, comprised of 41 and 31 dogs with tumor masses at their external genitalia and extragenital areas (e.g. skin and nasal cavity), respectively, were included in this study. The signalment of these 65 dogs and clinical history of 20 client-owned dogs were collected. Samples were taken by biopsy for both histopathological examination and FNA for cytological examination and diagnostic PCR. The PCR products from 10 apparently CTVT samples were purified and sequenced. Sixty-one CTVT cases were diagnosed by cytological and histological analyses, but 65 were positive by the PCR assay. Overall, the PCR assay improved the accuracy of diagnostic CTVT results, especially for the more difficult ETVT tumors. Moreover, this PCR-based approach can facilitate the decision as to discontinue chemotherapy by discrimination between residual tumor cell masses and fibrotic tissue.
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- 2016
25. Overexpression of chemokine ligand 7 is associated with the progression of canine transmissible venereal tumor
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Chiang Hsin-Chien, Wang Yu-Shan, Chou Chung-Hsi, Liao Albert Taiching, Chu Rea-Min, and Lin Chen-Si
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CXCL7 ,CXCR2 ,IL-6 ,TGF-β ,CTVT ,Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Chemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-β derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-β in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT). Results We have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1β and TGF-β had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression. Conclusion CXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target.
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- 2012
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26. How the devil facial tumor disease escapes host immune responses.
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Siddle, Hannah V. and Kaufman, Jim
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- *
CANCER treatment , *TASMANIAN devil , *IMMUNE response , *CD8 antigen , *CELL surface antigens - Abstract
The devil facial tumor disease (DFTD) is a contagious cancer that has recently emerged among tasmanian devils, rapidly decimating the population. We have recently discovered that DFTD cells lose expression of MHC molecules on the cell surface, explaining how this tumor avoids recognition by host CD8+T cells. [ABSTRACT FROM AUTHOR]
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- 2013
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27. Interaction between host and canine transmissible venereal tumor: diversity of mononuclear cells and major histocompatibility complex
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Duzanski, Anderson do Prado [UNESP], Universidade Estadual Paulista (Unesp), and Rocha, Noeme Sousa [UNESP]
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Vincristina ,MHC classe I e II ,MHC class I e II ,Cão ,TVTC ,Tumor cell immunity ,Vincristine ,Dog ,CTVT ,Imunidade celular tumoral - Abstract
Submitted by ANDERSON DO PRADO DUZANSKI null (andersonduzanski@hotmail.com) on 2017-08-25T19:27:59Z No. of bitstreams: 1 Dissertação - Defesa 01.08.17 final.pdf: 4614411 bytes, checksum: 932e6547164ff2bf33ba5b4da0ca7797 (MD5) Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-08-29T14:11:14Z (GMT) No. of bitstreams: 1 RESSALVA.pdf: 28248 bytes, checksum: fba755acd4371548d2037f9748ead918 (MD5) Made available in DSpace on 2017-08-29T14:11:14Z (GMT). No. of bitstreams: 1 RESSALVA.pdf: 28248 bytes, checksum: fba755acd4371548d2037f9748ead918 (MD5) Previous issue date: 2017-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) O tumor venéreo transmissível canino (TVTC) ocorre naturalmente em cães, sem predileção por raça ou sexo sendo transmitido durante o coito ou hábitos sociais. É também um tumor transplantável experimentalmente e tem sido utilizado como modelo para o estudo da relação entre tumor e hospedeiro. Apesar da maior infiltração inflamatória intratumoral e da expressão de moléculas do complexo principal de histocompatibilidade (MHC) estar associada à regressão do tumor, o papel central das células imunes do hospedeiro na evolução clínica do TVTC ainda não está claro. Neste estudo nós buscamos analisar a interação entre TVTC natural e hospedeiro, especialmente sob o ponto de vista da imunidade celular tumoral. Aqui nós identificamos e quantificamos por citometria de fluxo células T (CD3+, CD4+ e CD8+), células NK, células B, macrófagos, em amostras de sangue e de tumor, além da expressão imunoistoquímica de moléculas do MHC de classe I e II, sobretudo nas diferentes fases clínicas do tumor, assim como classificamos os subtipos citológicos do tumor e avaliamos o comportamento tumoral frente ao tratamento quimioterápico com sulfato de vincristina em uma amostra de 22 cães com TVTC natural. A quimioterapia foi efetiva no tratamento da maioria dos casos. Encontramos predomínio de TVTC linfocitóide e que metástases e resistência quimioterápica ocorreram apenas nos tumores de fenótipo linfocitóide e misto. Identificamos aumento significativo na expressão de moléculas de MHC classe I e II na fase de regressão. As células T CD3+ estavam igualmente presentes nas fases de progressão e regressão. Porém, as células T (CD4+ e CD8+), células NK e macrófagos estavam mais presentes na fase de regressão, enquanto as células B estavam em maior quantidade na fase de progressão, mas não foi possível correlacionar a fase clínica do tumor com um único tipo predominante de infiltrado inflamatório intratumoral. Ainda, a fase clínica e o subtipo citológico do tumor natural não pareceram ser determinantes na resposta ao tratamento quimioterápico, assim como não encontramos diferença imune expressiva entre os subtipos citológicos do tumor, indicando, portanto, não haver diferença quanto à interação tumor/hospedeiro. Nossos achados em citometria de fluxo mostram que a maior presença de células T no microambiente tumoral antes do início da quimioterapia não favoreceu a regressão do tumor, ao contrário da população macrofágica que parece ter contribuído para o menor número de sessões quimioterápicas. Identificamos ainda que cães fêmeas e cães de raça, em geral, apresentaram maior presença de células mononucleares circulantes e infiltrantes, e que as fêmeas mostraram evidência de resposta mais favorável à remissão completa do tumor acompanhada de quimioterapia em comparação aos cães machos, uma vez que as fêmeas apresentaram maior infiltrado intratumoral de macrófagos. Por fim, nossos dados não sustentam uma forte evidência de regressão espontânea no TVTC natural. Mais estudos são necessários para melhor entender os mecanismos da interação entre células do tumor e hospedeiras e a sua implicação na imunidade antitumoral, uma vez que, na ausência de tratamento o tumor natural provavelmente não regride espontaneamente, pois o sistema imune do cão parece ser requisitado pelo tumor durante os eventos biológicos associados à tumorigênese e ao escape da imunovigilância. The transmissible venereal canine tumor (CTVT) occurs naturally in dogs, without predilection for race or gender being transmitted during intercourse or social habits. It is also an experimentally transplantable tumor and it has been used as a pattern for the study about the relationship between the tumor and the host. Despite the greater intratumoral inflammatory infiltration and the expression of major histocompatibility complex molecules (MHC) is associated with tumor regression, the central role of host immune cells in the CTVT clinical evolution is not clear yet. In this study we sought to analyze the interaction between natural and host CTVT, especially from the point of view of tumor cell immunity. Here we identify and quantify by flow cytometry cells T (CD3+, CD4+ e CD8+), cells NK, cells B, macrophages, in blood and tumor samples, besides the immune histochemical expression of MHC class I and II molecules, specially in the different clinical phases of the tumor as well as classifying the cytological subtypes of the tumor and evaluating the tumor behavior against the chemotherapy treatment with vincristine sulfate in a sample of 22 dogs with natural CTVT. Chemotherapy was effective in the treatment of most cases. We found a predominance of lymphocytoid CTVT and that metastases and chemotherapeutic resistance occurred only in tumors of lymphocytoid and mixed phenotype. We identified a significant increase in the expression of MHC class I and II molecules in the regression phase. T CD3+ cells were also present in the progression and regression phases. However, T cells (CD4 + and CD8 +), NK cells and macrophages were more present in the regression phase, while B cells were more in the progression phase, but it was not possible to correlate the clinical phase of the tumor with a single type prevalent of infiltrated intratumoral inflammatory. Moreover, the clinical and cytologic subtype of the natural tumor did not appear to be determinant in the response to the chemotherapeutic treatment, nor did we find an expressive immune difference between the cytological subtypes of the tumor, indicating, therefore, that there was no difference in the tumor/host interaction. Our findings in flow cytometry show that the increased presence of T cells in the tumor microenvironment prior to the initiation of chemotherapy did not favor tumor regression, unlike the macrophagic population that appears to have contributed to the lower number of chemotherapy sessions. We also identified that female dogs and breed dogs in general had a higher presence of circulating and infiltrating mononuclear cells and that females showed evidence of a more favorable response to complete remission of the tumor accompanied by chemotherapy compared to male dogs, since females showed greater intratumoral infiltration of macrophages. Finally, our data do not support strong evidence of spontaneous regression in natural CTVT. More studies are necessary to better understand the mechanisms of interaction between tumor cells and hosts and their implication in antitumor immunity, since in the absence of treatment the natural tumor probably does not regress spontaneously, as the dog's immune system appears to be required by the tumor during the biological events associated with tumorigenesis and the escape of immunovigilance. CNPq: 445250/2014-3
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- 2017
28. Immunohistochemical, lectin histochemical and ultrastructural studies of canine transmissible venereal tumor in Brazil
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Paulo Vargas Peixoto, Regina Ruckert Ramadinha, Vivian de Assunção Nogueira, Ileana C. Miranda, Mariana Bezerra Mascarenhas, Ticiana N. França, Aníbal G. Armién, and Samay Zillmann Rocha Costa
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,microscopia eletrônica ,cão ,040301 veterinary sciences ,medicine.drug_class ,CTVT ,Biology ,Canine transmissible venereal tumor ,Monoclonal antibody ,0403 veterinary science ,03 medical and health sciences ,lectin histochemistry ,Antigen ,imuno-histoquímica ,ultrastructural ,medicine ,Tumor venéreo transmissível canino (TVTC) ,patologia ,lectino-histoquímica ,lcsh:Veterinary medicine ,General Veterinary ,Lectin ,04 agricultural and veterinary sciences ,medicine.disease ,030104 developmental biology ,Polyclonal antibodies ,Monoclonal ,immunohistochemistry ,dog ,biology.protein ,lcsh:SF600-1100 ,Immunohistochemistry ,pathology ,Antibody - Abstract
Canine transmissible venereal tumor (CTVT) is a naturally occurring contagious round-cell neoplasia, with poorly understood origin and transmission. This study aims to further investigate the tumor nature through immunohistochemistry, lectin histochemistry and transmission electron microscopy (TEM) analysis, and to provide support for diagnostic and differential diagnoses of CTVT. Immunohistochemistry was performed in 10 genital and six exclusively extragenital tumors, which were previously diagnosed by citology and histopathology. CTVT samples were incubated with biotinylated antibodies to specific membrane and cytoplasmic antigens (anti-lysozyme, anti-macrophage, anti-vimentin, anti-CD18, monoclonal anti-CD117, monoclonal anti-CD3, polyclonal anti-CD117, polyclonal CD3 and anti-CD79a), followed by the avidin-biotin-peroxidase complex technique. The lectins Con A, DBA, SBA, PNA, UEA-1, WGA, sWGA, GSL, JSA, PSA, PHA-L, PHA-E and RCA were additionally tested in four genital CTVTs and TEM was performed in eight genital tumors. The anti-vimentin antibody revealed strong immunoreactivity to neoplastic cells in all the assessed samples (16/16). The polyclonal anti-CD3 antibodies showed moderate to strong immunoreactivity in fourteen (14/16) and the polyclonal anti-CD117 in fifteen cases (15/16). There was no immunoreactivity to anti-lysozyme, anti-macrophage, anti-CD18, monoclonal anti-CD117, monoclonal anti-CD3 and anti-CD79a antibodies. At lectin histochemistry, it was observed strong staining of tumor cells to Con-A, PHA-L and RCA. There was no histopathological and immunoreactivity differences between genital and extragenital CTVTs. These findings do not support the hypothesis of histiocytic origin of CTVT. In contrast, the lectin histochemical results were similar to cells from lymphoid/myeloid origin. RESUMO: O Tumor Venéreo Transmissível Canino (CTVT) é uma neoplasia de células células redondas, contagiosa, com origem e transmissão ainda mal compreendidas. Com a finalidade de aprofundar a investigação sobre a natureza (origem) do TVTC, bem como fornecer subsídios para o estabelecimento do diagnóstico e diagnóstico diferencial, realizaram-se avaliações imuno-histoquímica, lectino-histoquímica e ultraestrutural de TVTC(s). A avaliação imuno-histoquímica foi feita em 10 TVTCs genitais e em 6 exclusivamente extragenitais previamente diagnosticados através de citologia e da histopatologia. Os TVTCs foram testados para reagentes específicos de antígenos de membrana e citoplasmáticos (anti-lisozima, anti-macrófago, anti-vimentina, anti-CD18, anti-CD3, anti-CD79, anti-CD117) com utilização da técnica complexo avidina-biotina-peroxidase. Adicionalmente, foram utilizadas as lectinas Con A, DBA, SBA, PNA, UEA-1, WGA, sWGA, GSL, SJA, PSA, PHA-L, PHA-E e RCA em quatro TVTCs genitais. Microscopia eletrônica foi realizada em oito TVTC genitais. Em 100% dos tumores testados (16/16) com anticorpo anti-vimentina (mono e policlonal) houve forte imuno-reatividade. Não houve reatividade para os anticorpos anti-lisozima, anti-macrófago, anti-CD18, anti-CD3, anti-CD79a e anti-CD117 quando empregamos anticorpos monoclonais, entretanto, com a utilização de anticorpos policlonais verificou-se marcação dos tumores com os anticorpos anti-CD3 e anti-CD117. Na avaliação lectino-histoquímica foi verificada forte marcação das células tumorais com Con-A, PHA-L e RCA. Não houve diferença histopatológica e de imuno-reatividade entre os TVTCs genitais e extragenitais. Estes achados não corroboram com a hipótese da origem histiocítica do CTVT (ausência de reatividade dos anticorpos anti-lisozima, anti-macrófago e anti-CD18), entretanto, os resultados da avaliação lectino-histoquímica foram em parte similares aos obtidos quando células de origem linfóide/mielóide (ConA, PHA-L e RCA) foram analisadas (Gimeno et al. 1995).
- Published
- 2017
29. The T963C mutation of TP53 gene does not participate in the clonal origin of canine TVT
- Author
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Vázquez-Mota, N., Simón-Martínez, J., Córdova-Alarcon, E., Lagunes, L., and Fajardo, R.
- Published
- 2008
- Full Text
- View/download PDF
30. In vitro Effect of Recombinant Feline Interferon-Ω (rFeIFN-Ω) on the Primary CanineTransmissible Venereal Tumor Culture.
- Author
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Setthawongsin C, Tangkawattana S, Rungsipipat A, and Techangamsuwan S
- Abstract
Background: Interferons (IFNs), signaling proteins produced by host cells, are secreted in response to pathogen activity as well as to tumor cells, and display antiviral, antiproliferative, and immunomodulatory effects. Recombinant feline interferon omega (rFeIFN-ω) has in vitro growth inhibition activities on various canine and feline tumor cell lines. Canine transmissible venereal tumor (CTVT) is used as an animal model for immunotherapy due to its specific growth phase. Previous studies have usually focused on the interaction between tumor infiltrating lymphocytes (TILs) and CTVT cells. However, the specific effects of rFeIFN-ω on CTVT cells remains poorly defined. Aims: The aims of this study, therefore, were to evaluate the in vitro effect of rFeIFN-ω on primary CTVT cells and to study the mRNA expression of apoptotic genes and drug resistance genes. Materials and Methods: Purified CTVT cells were treated with various concentrations of rFeIFN-ω and the viability of the cultured cells was ascertained at 24, 48, and 72 h post treatment (hpt) and a dose-response curve plotted. The mRNA expression of apoptotic ( BAX and BCL-2 ) and drug resistance ( ABCB1 and ABCG2 ) genes was performed by reverse transcription quantitative real-time PCR at 72 hpt. Results: rFeIFN-ω displayed an effect against CTVT cell viability, which decreasing viability in a dose-dependent manner within 72 hpt. The relative mRNA expression of BCL-2 was upregulated only at a rFeIFN-ω concentration of 10
4 IU/100 μl. However, higher concentrations of rFeIFN-ω gave a higher level of relative mRNA expression of ABCB1 transporter gene. Conclusion: This study provided the information of in vitro effect of rFeIFN-ω on CTVT cell viability in a dose dependent manner, as well as, the alteration of BCL-2 and ABCB1 gene expression after treatment. These results encourage future in vivo studies to evaluate the potential efficacy of this treatment in CTVT cases.- Published
- 2019
- Full Text
- View/download PDF
31. Immunohistochemical, lectin histochemical and ultrastructural studies of canine transmissible venereal tumor in Brazil
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Mariana B. Mascarenhas, Paulo V. Peixoto, Regina R. Ramadinha, Anibal G. Armien, Samay Z. Costa, Ileana C. Miranda, Vivian A. Nogueira, and Ticiana N. França
- Subjects
Canine transmissible venereal tumor ,CTVT ,immunohistochemistry ,lectin histochemistry ,ultrastructural ,dog ,pathology ,Veterinary medicine ,SF600-1100 - Abstract
ABSTRACT: Canine transmissible venereal tumor (CTVT) is a naturally occurring contagious round-cell neoplasia, with poorly understood origin and transmission. This study aims to further investigate the tumor nature through immunohistochemistry, lectin histochemistry and transmission electron microscopy (TEM) analysis, and to provide support for diagnostic and differential diagnoses of CTVT. Immunohistochemistry was performed in 10 genital and six exclusively extragenital tumors, which were previously diagnosed by citology and histopathology. CTVT samples were incubated with biotinylated antibodies to specific membrane and cytoplasmic antigens (anti-lysozyme, anti-macrophage, anti-vimentin, anti-CD18, monoclonal anti-CD117, monoclonal anti-CD3, polyclonal anti-CD117, polyclonal CD3 and anti-CD79a), followed by the avidin-biotin-peroxidase complex technique. The lectins Con A, DBA, SBA, PNA, UEA-1, WGA, sWGA, GSL, JSA, PSA, PHA-L, PHA-E and RCA were additionally tested in four genital CTVTs and TEM was performed in eight genital tumors. The anti-vimentin antibody revealed strong immunoreactivity to neoplastic cells in all the assessed samples (16/16). The polyclonal anti-CD3 antibodies showed moderate to strong immunoreactivity in fourteen (14/16) and the polyclonal anti-CD117 in fifteen cases (15/16). There was no immunoreactivity to anti-lysozyme, anti-macrophage, anti-CD18, monoclonal anti-CD117, monoclonal anti-CD3 and anti-CD79a antibodies. At lectin histochemistry, it was observed strong staining of tumor cells to Con-A, PHA-L and RCA. There was no histopathological and immunoreactivity differences between genital and extragenital CTVTs. These findings do not support the hypothesis of histiocytic origin of CTVT. In contrast, the lectin histochemical results were similar to cells from lymphoid/myeloid origin.
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32. How the devil facial tumor disease escapes host immune responses
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James C. Kaufman and Hannah V. Siddle
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contagious cancer ,Immunology ,Population ,CTVT ,Disease ,DFTD ,Biology ,Major histocompatibility complex ,Immune system ,Interferon ,Tasmanian devil ,medicine ,Immunology and Allergy ,education ,Author's View ,education.field_of_study ,epigenetics ,extinction ,conservation ,Cancer ,transmissible tumor ,interferon ,medicine.disease ,Oncology ,biology.protein ,MHC ,CD8 ,medicine.drug - Abstract
The devil facial tumor disease (DFTD) is a contagious cancer that has recently emerged among Tasmanian devils, rapidly decimating the population. We have recently discovered that DFTD cells lose the expression MHC molecules on the cell surface, explaining how this tumor avoids recognition by host CD8+ T cells.
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- 2013
33. Canine transmissible venereal tumors: Aspects related to programmed cell death
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Stockmann, Daniela [UNESP], Ferrari, Heitor F. [UNESP], Andrade, Alexandre L. [UNESP], Lopes, Rodrigo A. [UNESP], Cardoso, Tereza C. [UNESP], Luvizotto, Maria C.R. [UNESP], and Universidade Estadual Paulista (Unesp)
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Dog ,Apoptosis ,Ctvt ,Canis familiaris ,Sticker's sarcoma - Abstract
Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:25:51Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:25:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-04-18 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. UNESP - University of São Paulo State Faculdade de Medicina Veterinária Laboratory of Virology UNESP Faculdade de Medicina Veterinária Laboratory of Animal Pathology UNESP - University of São Paulo State Faculdade de Medicina Veterinária Laboratory of Virology UNESP Faculdade de Medicina Veterinária Laboratory of Animal Pathology
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- 2011
34. Prevalence of different cytomorphological types of transmissible venereal tumours and the association with prognosis in dogs treated with vincristine sulphate – Retrospective study
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Maria Isabel Mello Martins, Cristiane Sella Paranzini, Marcos César Sant’anna, and Giovana Wingeter Di Santis
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medicine.medical_specialty ,Pathology ,Chemotherapy ,Vincristine ,business.industry ,medicine.medical_treatment ,Prognosis ,Prevalence ,CTVT ,Retrospective cohort study ,Drug resistance ,lcsh:S1-972 ,Pharmacotherapy ,Epidemiology ,medicine ,lcsh:Agriculture (General) ,Cytology ,General Agricultural and Biological Sciences ,business ,Histiocyte ,medicine.drug - Abstract
Canine transmissible venereal tumours (CTVT) are the most commonly diagnosed tumours in veterinary hospitals. CTVT is morphologically classified as a round cell tumour, although the exact origin of the cells is unknown. Immunohistochemical studies have suggested histiocytic and mesenchymal origin. CTVT can be classified as lymphocyte-like, plasmocyte-like, and mixed according to their cytomorphological features. The treatment of choice for CTVT is chemotherapy with vincristine sulphate applied weekly; this produces a good prognosis. However, an increase in the number of chemotherapy applications and adjuvant therapies has become common. The aim of this study was to determine the association of cytomorphological types of CTVT with resistance and partial resistance to vincristine sulphate and the possible need for a large number of chemotherapy sessions. A retrospective study of a 24-month period evaluated 46 diagnosed and treated cases of CTVT. It was concluded that there is a higher prevalence of plasmacyte-like, followed by mixed and lymphocyte-like CTVT. The cytomorphological type did not differ in relation to the response to the treatments with vincristine sulphate and the number of chemotherapy sessions necessary for CTVT regression has increased by factors not yet elucidated.
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- 2015
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35. Overexpression of chemokine ligand 7 is associated with the progression of canine transmissible venereal tumor
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Rea-Min Chu, Yu-Shan Wang, Chen-Si Lin, Albert Taiching Liao, Chung-Hsi Chou, and Hsin-Chien Chiang
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TGF-β ,Male ,Chemokine ,DNA, Complementary ,CTVT ,Canine transmissible venereal tumor ,Dogs ,medicine ,Animals ,CXC chemokine receptors ,Dog Diseases ,RNA, Messenger ,Interleukin 6 ,Cells, Cultured ,Venereal Tumors, Veterinary ,IL-6 ,lcsh:Veterinary medicine ,CXCR2 ,General Veterinary ,biology ,Tumor-infiltrating lymphocytes ,Interleukin-6 ,Interleukin ,General Medicine ,medicine.disease ,veterinary(all) ,Gene Expression Regulation, Neoplastic ,CXCL7 ,Immunology ,biology.protein ,Cancer research ,lcsh:SF600-1100 ,Chemokines, CXC ,Transforming growth factor ,Research Article - Abstract
Background Chemokines play multiple roles in the development and progression in a variety of tumors. Chemokine (C-X-C motif) ligand 7 (CXCL7) has been found associated with pro-inflammatory responses, but its role in cancer growth remains unclear. Our previous study showed that R phase tumor infiltrating lymphocytes (TILs) produced large amounts of interleukin (IL)-6 which antagonized transforming growth factor (TGF)-β derived from CTVT to diminish the immune-suppressive microenvironment. Now we intend to determine the expression pattern of CXCL7 and the role of IL-6/TGF-β in CXCL7 induction during spontaneous progressive (P) and regressive (R) phases in canine transmissible venereal tumor (CTVT). Results We have demonstrated that CXCL7 expressed at high level in P phase and down-regulated in R phase by western blot and real-time PCR. This suggested that CXCL7 expression was negatively correlated with the tumor growth. Co-culturing TILs with CTVT cells was found to reduce CXCL7 expression, while adding IL-6 blocking antibody reversed it. Moreover, in P phase CTVT, while IL-1β and TGF-β had no obvious effect on CXCL7 expression, IL-6 was found significantly to reduce CXCL7 expression in a dose-dependent manner. The mRNA expression results of CXCL7 receptor, CXCR2, further confirmed the effects of IL-6 concentration on the CXCL7 expression. Conclusion CXCL7 overexpression might be associated with the progressive growth of CTVT. The results shown here also suggest the role of CXCL7 in cancer development and the potential as the anti-cancer therapeutic target.
- Published
- 2012
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