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A 5-year-old spayed female mixed-breed dog was referred to the Atlantic Veterinary College (Charlottetown, Prince Edward Island) because of a 7-month history of intermittent pink, mucoid, vulvar discharge. The dog was imported from the Bahamas at 3.5 y of age and had a history of transmissible venereal tumor (TVT) of the vulva that was successfully treated with a course of vincristine chemotherapy. Complete remission was achieved with a disease-free interval of 6 mo before clinical signs recurred. Abdominal ultrasound and CT scan identified a large caudal abdominal mass thought to arise from the uterine stump. An exploratory laparotomy was performed and the mass grossly excised. Histopathology was consistent with a poorly differentiated round cell tumor, and immunohistochemical analysis confirmed TVT as the most likely diagnosis. No further treatment was carried out. Repeat abdominal ultrasound at 4 mo after surgery showed no evidence of mass recurrence. At 8 mo after surgery, the dog was reported to be doing well clinically. Key clinical message: Transmissible venereal tumor should be considered as a differential diagnosis for masses arising from the deep genital tissues of dogs in cases where there is a history of previous TVT. Transmissible venereal tumor should be considered even in dogs that have had complete resolution of a primary mass after chemotherapy., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: The ocular side effects of cancer chemotherapeutic drugs are relatively uncommon. Nonetheless, the ocular system has a potentially high sensitivity to toxic substances. This study proposed a framework to assess the effect of vincristine chemotherapy on intraocular pressure, tear protein, and oxidative stress in canines with transmissible venereal tumor (TVT)., Methods: The study group comprised 10 dogs with TVT, whose diagnosis was based on cytology, and all dogs were treated with vincristine for 4 weeks. Each animal was given a complete ophthalmic examination, followed by a standard Schirmer tear test. Before and 20 min after administering vincristine, intraocular pressure (IOP) was measured in the eyes with a noncontact tonometer. At any of the times mentioned, tear samples were collected using the Schirmer test procedure and were subjected to protein analysis-oxidative stress index (OSI), total antioxidant capacity (TAC), total oxidant status (TOS), nitric oxide (NO), and malondialdehyde (MDA) were determined, and standard statistical analysis was applied., Results: No significant differences were found in protein in tears, but mean Pre and Postinjection IOP revealed a significant decrease in the eyes each week. Also, results indicated significant differences in oxidative stress markers: increased OSI, NO, and MDA, and reduced TAC., Conclusion: The importance of an increase in oxidative stress levels in the tears of vincristine-treated patients should be taken seriously, as it appears to play a role in the pathogenesis of eye disease. Therefore, during the treatment weeks prior to prescribing vincristine, eye diseases should be evaluated and considered., (© 2023 American College of Veterinary Ophthalmologists.)

Canine transmissible venereal tumour (CTVT) is a contagious cancer spread by transfer of living cancer cells. Occasional cases are observed in the UK in dogs imported from endemic regions. Here, we report a case of imported canine transmissible venereal tumour that was transmitted to a second dog within the UK. Transmission of genital canine transmissible venereal tumour occurred despite neutered status of the second dog. The aggressive course of disease in both cases, which included metastasis, resistance to therapeutic interventions and ultimate euthanasia of both dogs, is described. The diagnosis of canine transmissible venereal tumour was made using a combination of cytology, histology, immunohistochemistry and PCR to detect the LINE-MYC rearrangement. Practitioners unfamiliar with canine transmissible venereal tumour are reminded of this disease of concern, particularly when imported dogs are placed in multi-dog households, irrespective of neuter status., (© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

The aim of this study is to evaluate the effects of scheduled vincristine sulfate therapy on canine oocyte quality and nuclear oocyte maturation, associated with total antioxidant and oxidant status of ovaries and Anti-Müllerian Hormone (AMH) concentrations in dogs with Canine Transmissible Venereal Tumor (CTVT). Six bitches suffering from CTVT and six healthy bitches were included in the study. Hemogram was carried out weekly. AMH measurements and ovariohysterectomy operations were performed after the termination of vincristine sulfate therapies. Tissue samples from ovaries were utilized for Malondialdehyde (MDA), reduced Glutathione (GSH), Superoxide Dismutase (SOD), Total Anti-oxidative Status (TAS), Total Oxidative Status (TOS) measurements, and Oxidative Stress Index (OSI) was calculated. Collected oocytes were evaluated for meiotic competence, after In Vitro Maturation (IVM) and parthenogenetic activation. No difference between the two groups was observed in hematologic parameters (P > 0.05). Meiotic stages of Germinal Vesicle Break Down (GVBD), Metaphase I (MI), and Metaphase II (MII) were significantly different between groups (P < 0.05). The number of oocytes reaching MII and meiotic resumption was lower in the CTVT group. Furthermore, AMH concentrations, oxidant parameters (OSI, TOS, and MDA), and antioxidant parameters (GSH, SOD, and TAS) were also statistically different between groups (P < 0.05). The results of this study show that vincristine sulfate application in the treatment of CTVT could alter oxidant/antioxidant status in ovaries. Apart from these, oocyte quality and IVM rates seem to decline related to gonadotoxicity. Moreover, AMH could be an important marker in the evaluation of oocyte qualities in bitches, as it is in women., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Transmissible venereal tumors (TVT) are a wide range of canine tumors for which there are no effective markers to monitor the therapeutic response in real-time. Circulating biomarkers can be valuable in early cancer diagnosis and prognosis. Accordingly, this study aimed to investigate the significance of the cell-free DNA (cfDNA) and cfDNA integrity index to monitor the response of TVTs to vincristine and compare them with lysyl oxidase activity. Plasma and sera were collected from fifteen male dogs within four weeks before drug administration. The analytical method was mainly based on the quantitative polymerase chain reaction (qPCR) technique for short and long cfDNAs and lysyl oxidase activity was measured in serum., Results: The results of the cfDNA integrity index showed a significant (p < 0.05) difference in the baseline concentration compared to the second and third weeks (with cut-off values of 1.118 and 93.33% specificity). The cfDNA integrity index increased over time due to the reduction of short cfDNAs in the first week after treatment. Lysyl oxidase activity increased during the fourth week (p < 0.001), but there were no significant differences in the other weeks compared to the baseline. The ROC analysis of lysyl oxidase revealed high sensitivity (100%) and specificity (90%) on the second and third weeks compared to the baseline. Multivariate analysis between cfDNA integrity index and lysyl oxidase showed significant correlation (p < 0.05) only in baseline results., Conclusions: Overall, short cfDNA, the cfDNA integrity index, and lysyl oxidase activity can be proposed as diagnostic biomarkers and putative prognostic candidates in TVT patients. These biomarkers can be combined with cytology to quickly diagnose TVT., (© 2022. The Author(s).)

A 2-year-old male neutered mixed breed dog was referred for evaluation of left-sided unilateral epistaxis and mucoid discharge following adoption from Mexico 2 months prior to presentation. Computed tomography (CT) showed soft tissue that filled the entirety of the left nasal passage with mild turbinate loss. Subsequent rhinoscopy revealed multifocal patches of discrete, white, wispy, vascularized abnormal tissue in the left nasal cavity. Cytology and histopathology procured with rhinoscopic-guidance were suspicious for transmissible venereal tumor (TVT). Confirmation of a TVT diagnosis was made with polymerase chain reaction for the long interspersed element inserted upstream of the c-myc gene. The dog was treated with 4 cycles of vincristine (0.5 mg/m 2 , IV, once every 7 days) with complete and sustained resolution of clinical signs shortly after the third cycle. Nasal TVT in dogs is an uncommon presentation of a neoplasm that primarily results in genital or oral lesions. There is a void in the veterinary literature regarding the rhinoscopic appearance, as well as limited clinical descriptions of nasal TVT. Therefore, the objectives of this report were to provide a detailed description of the rhinoscopic appearance of a canine nasal TVT, in addition to clinical features, diagnostic findings, CT imaging, and successful therapeutic management., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was a retrospective analysis of clinical manifestation and treatment outcome of the nasal form of transmissible venereal tumours (TVT)., Material and Methods: Twelve dogs suffering from nasal TVT were included in this study. Patients with primary genital lesions were excluded from the study. Signalment, physical examination and laboratory findings, results of further diagnostics, and treatment results were recorded in all patients., Results: The study population comprised 9 male and 4 female dogs with an (estimated) age ranging from 3 to 7 years. With one exception all dogs originated from Ukraine. Symptoms of nasal TVT included sneezing, nasal bleeding (all cases), skull infiltration (9 cases), oronasal fistulas (9 cases) and cutaneous fistulas (5 cases). Animals received vincristine sulfate at 0.7 mg/m 2 i. v. weekly. The treatment course consisted of 4-9 cycles (median 5 cycles). Complete remission was achieved in all cases. All dogs were disease-free during the follow-up period (median 23.5 months, range 12-56 months). All patients tolerated the treatment very well., Clinical Significance: In conclusion, our data suggest that nasal TVT can have a good response to vincristine treatment. TVT should be considered as a differential diagnosis in sneezing dogs with nasal discharge or bleeding especially in young dogs and in dogs with suspected nasal tumours, even in countries without a stray animal population., Competing Interests: The authors confirm that they do not have any conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Vincristine is the first-line drug for the chemotherapy of canine transmissible venereal tumor (CTVT). Drug resistance is related to tumor cyto-morphological patterns of CTVT. There are anti-cancer properties of ivermectin, thus, a combination of ivermectin and vincristine could be an effective chemo-therapeutic treatment regimen for CTVT. Study aims, therefore, were to (1) assess the frequency of CTVT cyto-morphologies, and (2) evaluate treatment efficacy and possible adverse reactions to vincristine compared with a combination vincristine and ivermectin. Dogs (n = 41) with CTVT were characterized by tumor cyto-morphology and disease severity and of those, 20 were randomly allocated into two groups. There was a control group (G-Vin; n = 10) in which there was treatment with vincristine; and an experimental group (G-Iv/Vin; n = 10) in which there was treatment with the ivermectin/vincristine combination. Although dogs in the G-Iv/Vin group had more severe disease at the beginning of the study (P = 0.0031), the number of weeks and chemotherapy sessions until tumor remission were similar among dogs of the two groups, indicating both treatments were effective. There was a decrease in the leukocyte counts (P = 0.0020), related to neutropenia (P = 0.0371) in the G-Vin but not the G-Iv/Vin treatment group. There was no tumor resistance that developed during the study regardless of the treatment regimen used or tumor cytomorphology. In summary, the use of the vincristine/ivermectin combination was well tolerated and efficacious for CTVT treatment., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Canine transmissible venereal tumors (CTVTs) generally have different cytomorphologic subtypes and phases of progression. Some tumors have variable biologic behavior including a progressive increase in tumor aggressiveness and variable responses to chemotherapy. This behavior is partially due to high p-glycoprotein expression by tumor cells, which leads to the expulsion of chemotherapeutic drugs. Other possible causes include changes in pro- and anti-apoptotic genes from the BCL-2 family and DNA repair systems, which are associated with the p53 gene family., Objectives: We aimed to determine the relative expression of the multi-drug resistance 1 (MDR1), p53, b-cell lymphoma 2 (BCL2), and bcl 2-associated X (BAX) genes in CTVT before and after therapy and establish a relationship with treatment responses, cytomorphologic patterns, and tumor progression identified with histopathology., Methods: RT-qPCR was performed on 21 CTVT tumor samples before and after initiating chemotherapy to determine specific gene expression. Normal canine testicular tissue was used as a negative control for all experiments., Results: MDR1 expression was decreased before and after initiating vincristine therapy in CTVT tumor tissues compared with normal canine testicular tissue; p53 and BAX were overexpressed at both time points compared with normal tissue, and no statistical differences were seen between the different morphologic types. However, BAX expression was decreased in the group with quick therapeutic responses but was still overexpressed compared with normal testicular tissue. In the group with the slowest chemotherapeutic responses, BCL2 was overexpressed., Conclusion: The findings of this study showed a relative increase in MDR1 gene expression in response to chemotherapy and higher expression in plasmacytoid CTVTs compared with the other cytomorphologic patterns. BCL2 overexpression was related to a favorable prognosis, and p53, BAX, and BCL2 were expressed independent of the cytomorphologic CTVT type. All of the genes were expressed independent of tumor progression, as noted on histopathology., (© 2019 American Society for Veterinary Clinical Pathology.)

Canine transmissible venereal tumour (CTVT) is frequently reported in dogs and is responsible for high morbidity rates and economic losses. Three clinical cases were presented at the clinic of the Faculty of Veterinary Medicine, University of Tripoli. One male and two female German shepherds were diagnosed with CTVT based on case history and tumor shape. The diagnosis was confirmed by histopathological examination. The dogs were treated with vincristine intravenously at a dose of 0.025 mg/kg and recovered fully within 4 weeks. All three dogs remained alive with no evidence of recurrence. These first cases of CTVT reported from Libya show the importance of combining case history, clinical examination and laboratory confirmation to arrive at a definitive diagnosis and implement effective therapy., Competing Interests: The authors declare that there is no conflict of interest.

Canine transmissible venereal tumour (CTVT) is a naturally occurring contagious neoplasm of dogs located mainly on the external genitalia of both sexes. The course of vincristine chemotherapy, the most effective and practical therapy, is affected by the immune status of the host. The aim was to investigate recombinant human interferon alpha-2a (rhIFNα-2a) and vincristine for treatment of CTVT. A total of 21 female dogs were included. In group I (n = 9), vincristine (0.025 mg/kg, IV) was administered weekly. In group II (n = 6), dogs were injected intratumorally weekly with 1.5 million IU rhIFNα-2a. In group III (n = 6), rhIFNα-2a and vincristine were combined. No tumour regression was observed after three injections of rhIFNα-2a in group II and weekly vincristine was administered. The number of tumour infiltrating lymphocytes (TILs), mitotic figures and apoptotic cells were counted in subsequent incisional tumour biopsies. The Kaplan-Meier Method was used to analyse survival using complete tumour regression as the outcome and Breslow Test was used for comparison of survival curves. Differences in TILs, cell proliferation and apoptosis between groups were assessed by analysis of covariance. Complete regression was observed in all animals included. Mean duration of vincristine treatment for complete regression was shorter in group II (3.50 weeks, 95% CI, 3.06-3.94, P < 0.05) and group III (3.17 weeks, 95% CI, 2.84-3.49, P < 0.01) compared to group I (5.11 weeks, 95% CI, 4.42-5.80). Vincristine and rhIFNα-2a combination increased TILs in CTVT biopsies compared to vincristine treatment (P = 0.017) and vincristine treatment after rhIFNα-2a (P = 0.049). Vincristine treatment after rhIFNα-2a (Group II; P < 0.001) and rhIFNα-2a and vincristine combination (Group III; P < 0.001) decreased apoptosis. The results indicate that intratumoral rhIFNα-2a treatment alone is not effective in CTVT. However, combination of rhIFNα-2a and vincristine shortens the duration of treatment compared to vincristine therapy., (© 2018 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

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., (© 2018 John Wiley & Sons Ltd.)

A two-year-old, female intact, cross-breed dog presented with a two-month history of nasal discharge. Computed tomography (CT) demonstrated obliteration of both nasal cavities by soft tissue density, destruction of the nasal and ethmoidal turbinates, and lysis of the frontal and palatine bones and maxilla. Frontal sinuses and maxillary recesses were obscured by soft tissue/fluid density. Histopathological examination of the mass was diagnostic of transmissible venereal tumor. The dog was clinically normal 3 months after treatment initiation with vincristine sulphate and amoxicillin/clavulanate. Six months after the completion of treatment no mass-like lesion was demonstrated in CT sections. Nasal cavities, maxillary recesses and frontal sinuses were filled with air. The reticular turbinate nasal plexus appeared atrophic with focal loss of the nasal turbinates on both sides. The ethmoidal turbinates were well-defined; however, focal loss of turbinates was also seen. Lysis of the frontal and palatine bones were still evident.

The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylation, and functional pathway analyses on serial biopsies of vincristine-treated CTVTs and found that regression occurs in sequential steps; activation of the innate immune system and host epithelial tissue remodeling followed by immune infiltration of the tumor, arrest in the cell cycle, and repair of tissue damage. We identified CCL5 as a possible driver of CTVT regression. Changes in gene expression are associated with methylation changes at specific intragenic sites. Our results underscore the critical role of host innate immunity in triggering cancer regression., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2016 John Wiley & Sons Ltd.)

Canine transmissible venereal tumour (CTVT) is a contagious venereal tumour of dogs, commonly observed in dogs that are in close contact with one another, or in stray and wild dogs that exhibit unrestrained sexual activity. CTVT represents a unique, naturally transmissible, contagious tumour, where the mutated tumour cell itself is the causative agent and perpetuates as a parasitic allograft in the host. Clinical history, signalment and cytological features are often obvious for establishing a diagnosis though biopsy and histological examination may be needed in atypical cases. Most cases are curable with three intravenous injections of vincristine sulphate at weekly intervals. The role of stray and wild dogs makes the disease difficult to control and necessitates sustained animal birth control in stray dogs along with prompt therapy of the affected dogs. This review captures the manifold developments in different areas embracing this fascinating tumour, including its biology, diagnosis and therapeutic alternatives., (© 2013 John Wiley & Sons Ltd.)

Aim: To improve treatment of inoperable transmissible venereal tumors (TVTs) in dogs. Recently, we showed that TVT is sensitive to intratumoral treatment with interleukin-2 (IL2). In addition it is known that TVT is sensitive to intravenous treatment with vincristine. In the present study we tried to establish the therapeutic effect of intratumoral treatment with vincristine and IL2., Patients and Methods: We treated 12 dogs with TVT with 1-4 intratumoral treatments with vincristine and IL-2. Per treatment we used vincristine (0.5-0.7 mg/m(2)) and IL2 (2×10(6) units). The injections were given at weekly intervals., Results: Early therapeutic effects were: three complete regressions, four partial regressions, three stable disease, and two progressive disease. Late therapeutic effects were established 45-60 months after the first presentation; there were five complete regressions, no partial regressions, nor stable or progressive diseases. Interestingly, all five dogs with late therapeutic effects were in good health. No tumor recurrence was noted., Conclusion: Intratumoral treatment of TVT with vincristine and IL2 appears to have impressive therapeutic effects., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m(2) of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m(2) were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug's clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.

In this study, 12 dogs affected by canine transmissible venereal tumor (CTVT) and testicular seminoma tumor were studied retrospectively. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, and masses were surgically removed. The tumors were grossly examined, and sections of 4-μm thick were obtained from each sample and stained with H&E. For chemotherapy, vincristine sulfate was administered weekly as an infusion over 3 min via the cephalic vein at a dose of 0.025 mg/kg after diluting with physiological saline to a total amount of 10 ml. If no remission was observed after 8 weeks, chemotherapy was continued with weekly doxorubicin infusion at a dose of 1 mg/kg. All the tumor samples were divided into four cytohistopathologic groups, namely: multilobular (six cases), papillary (two cases), pedunculated (two cases), and tubular (two cases of seminoma). The most frequently represented tumor type was multilobular (6/10, 60 %) followed by pedunculated (2/10, 20 %), papillary (2/10, 20 %), and tubular (two cases of seminoma, 100 %). Cytological smears from eight tumors in regression after chemotherapy were poorly cellular, and many cells were fragmented. In two progressive tumors, there was an average of 1,406 ± 972 CTVT 200 cells/μl or 96.71 % of total cells counted. Thus, tumor cells represented 96.71 % of total cells within the biopsy specimens and the leukocytes 4.29 % (leukocyte, tumor cell ratio=0.062 ± 0.031). In eight regressive tumors, there was an average of 1,245 ± 1,032 CTVT 200 cells/μl or 97.31 % of total cells counted. Thus, tumor cells represented 97.31 % of total cells and leukocytes 2.69 % (leukocyte, tumor cell ratio=0.071 ± 0.174). Our data suggested that combination treatment with vincristine and doxorubicin in the future could be an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, and also, treatment success could easily be followed by the cytological changes.

A Dalmatian female presented with a history of vaginal bleeding and was diagnosed as having transmissible venereal tumour (TVT) after cytological examination of the vaginal growth revealed typical TVT cells. A cytology of the aspirate from multiple nodules in the skin near the abdominal and inguinal pair of mammary glands revealed similar cells suggestive of metastasis to skin of mammary region. Chemotherapy was initiated with weekly injections of vincristine sulphate (0.025 mg/kg BW, IV, SID) and haematological examination was performed pre- and post-treatment to assess the prognosis of the patient and side effects of the drug. The major side effects observed during the course of the treatment were high body temperature, mild neutropaenia and significant decrease in packed cell volume, haemoglobin, total leucocyte and erythrocyte count. Four weekly injections of vincristine were administered, and 4 weeks from initiation of treatment, the tumour and nodules were gone, suggesting complete recovery., (© 2012 Blackwell Verlag GmbH.)

We investigated eight adult dogs that were brought to veterinary clinics with a history of transmissible venereal tumors (TVT). Our goal was to demonstrate the occurrence of apoptosis and the cessation of cell proliferation at every phase of scheduled chemotherapy for naturally occurring TVT. Tissue samples were collected immediately after weekly treatments with vincristine sulfate and processed for histological purposes. Sections 5 μm thick were stained by the TUNEL reaction for apoptosis and immunostained for Ki67 as a proliferation marker. We observed that after vincristine applications, tumor cell proliferation ceased and apoptosis increased. Ki67 HSCORE values were significantly lowered after the first and second treatments with the chemotherapeutic agent compared to controls, whereas TUNEL HSCORE values were significantly higher after two applications of vincristine compared to controls. Our results suggest that scheduled vincristine sulfate applications stabilize the induction of tumor regression by inducing apoptosis and preventing cell proliferation.

Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression., (2008 Elsevier Ltd. All rights reserved.)

Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was assessed. Tumour biopsies were taken weekly to evaluate histological changes. Complete tumour regression was observed in all the dogs treated with BCG, vincristine and BCG/vincristine combination therapy. BCG/vincristine combination therapy had a statistically significantly shorter regression time than BCG or vincristine therapy. No tumour regression was observed in the control group. Intratumoral BCG treatment resulted in the appearance of macrophages and increased numbers of tumour infiltrating lymphocytes (TILs) followed by tumour cell apoptosis and necrosis. Treatment with vincristine resulted in increased tumour cell apoptosis, reduction in the mitotic index and a decrease in the number of TILs. Tumours from dogs on BCG/vincristine combination were characterised by reduction in the mitotic index, and appearance of numerous TILs and macrophages followed by marked tumour cell apoptosis and necrosis. This study indicates that combined BCG and vincristine therapy is more effective than vincristine in treating CTVT, suggesting that the clinical course of this disease may be altered by immunochemotherapy.

Sticker's sarcoma (also known as transmissible venereal tumor) is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT), treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy). Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 mus each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

An 11-month-old prepubertal crossbreed female dog was presented with multiple nodular lesions disseminated over the cervical, back, flank, and abdominal regions. The lesions were ulcerated and cauliflowerlike, or nodular and subcutaneous, measuring up to 13 cm in diameter. Cytologic preparations of one of the lesions revealed a uniform population of round to oval cells, with lightly basophilic cytoplasm that contained multiple distinct vacuoles. Frequent mitotic figures and occasional lymphocytes were also observed. The cytologic diagnosis was cutaneous transmissible venereal tumor (TVT) in a progressing growth phase. This was confirmed by histologic and immunohistochemical findings. Vaginal TVT was diagnosed later in the dog's mother. TVT is a contagious neoplasm of sexually mature dogs that usually is transmitted by coitus and affects the genital mucosa. To our knowledge, this is the first report of naturally occurring multicentric TVT in a prepubertal female dog and also is unique in its exclusively cutaneous (no mucosal) involvement. We speculate that transmission of neoplastic cells occurred during cohabitation and social/mothering behavior between the dogs. Despite the atypical clinical presentation, response to chemotherapy with vincristine was excellent, leading to complete regression of the neoplasm without relapse after 6 months.

Purpose: To determine whether larger confluent zones of ablation can be achieved in chemical ablation with use of a multiple-tine infusion device compared with standard needle infusion in a solid tumor model., Materials and Methods: Multiple canine venereal sarcomas (N=42) were implanted in nine mildly immunosuppressed dogs (treated with 10 mg/kg cyclosporin A twice daily). Tumors incubated for 8-12 weeks grew to a diameter of 5.4 cm+/-1.0. With ultrasound guidance, 8-56 mL of 100% ethanol or 15% acetic acid (diluted in saturated saline solution) were injected in aliquots (2-8 mL) at multiple distances (radius of 0-2 cm) from the needle axis with use of a multiple-tine infusion device. Presence of fluid reflux at the needle puncture site and resultant coagulation diameters were measured within 1 hour and compared with the results of infusion with a standard 18-gauge needle., Results: Multiple-tine infusion enabled greater fluid infusion (15 mL+/-3 to 53 mL+/-3 depending on protocol) than standard needle injection (8 mL+/-1) before reflux was observed at the puncture site (P<.01). Additionally, progressive gains in contiguous tumor coagulation were achieved because acetic acid was infused as far as 2 cm from the needle axis with the multiple-tine device (P<.01; R(2)=0.59; y=0.5x+2.9). Optimal coagulation was achieved with the infusion of 4-mL aliquots at 0.5 cm and 1.0 cm from the needle, followed by three 4-mL or 8-mL aliquots (40 degrees rotation between infusions) at 1.5 cm and 2.0 cm from the needle (32 mL+/-0 and 53 mL+/-3 total, respectively). This yielded confluent short-axis coagulation diameters of 4.9 cm+/-1.0 and 5.4 cm+/-1.0, respectively, which were significantly greater than the measurement of 3.1 cm+/-0.4 achieved with standard needle infusion (P<.01). Smaller and noncontiguous foci of coagulation foci (1.7 cm+- 0.5) were seen with the use of ethanol for standard needle and multiple-tine infusions., Conclusions: Chemical ablation with 15% acetic acid with use of a multiple-tine infusion device resulted in larger diameters of contiguous tumor coagulation and enabled greater volumes of infusion than standard needle infusion or ethanol ablation. This suggests that chemical ablation with acetic acid infused with use of a multiple-tine device may overcome some of the difficulties seen with the use of conventional needle chemical ablation injection alone, such as irregular ablation and fluid reflux up the needle tract.

The effectiveness of Doxil as a new chemotherapeutic agent against canine transmissible venereal tumor was evaluated, using NOD/ SCID and CD1-nu xenograft mouse models and the response between the two mouse strains was compared. Samples of xenografted venereal tumor were inoculated SC into 20 six week-old NOD/SCID mice and 20 six week-old CD1-nu mice. Seven weeks later, tumor-bearing mice were divided into treatment and control groups. Treatment group was injected with Doxil (6 mg/kg, IP, as a single injection). Control group was injected with buffered saline (0.75cc, IP). Tumor size was determined by caliper measurements and tumor response was assessed according to standard criteria. In both strains there was a significant decrease in tumor size in response to Doxil treatment (P<0.0001). In CD1-nu eight out of nine tumors (88%) responded to the treatment, and in 2 cases complete remission was observed. In NOD/SCID group response to the treatment was seen in eight out of ten tumors (80%) but none regressed fully. Response to the treatment was statistically equal in both strains even though the apoptotic rate, confirmed by TUNEL staining, was higher in NOD/SCID than in CD-1-nu (8.65% and 0.7%, respectively) and tumor infiltrating cells were different: eosinophils in NOD/SCID and CD45R-positive B lymphocytes, and plasma cells in CD-1-nu. In untreated CD1-nu mice, tumor progress was slower than in NOD/SCID. Our results indicate that Doxil is effective against CTVT in mouse xenograft models.

Transmissible venereal tumour (TVT) is a coitally transmitted neoplasm of dogs and is common among sexually active dogs, where sexual behaviour is not under control. Several treatment options are available for the treatment of the tumour, with chemotherapy being the most commonly employed. In this study, we investigated the clinical and cytological changes after weekly vincristine sulphate administration in 38 cases of naturally occurring TVT. Tumours totally regressed in 31 dogs after two to seven doses (mean 3.54 +/- 1.01) of vincristine. One dog died after the fifth dose of vincristine, and in six dogs, an additional treatment with doxorubicin was needed. Masses were still present in four dogs and the histopathological examination revealed small nodules of granulation tissue in two dogs, while viable tumour cells were identified in the remaining two cases. No recurrences were observed in a follow-up period of 7-49 months (mean 13.64 +/- 9.66); in one dog, granulation tissue was detected in the surgery site after 2 months. Treatment success could easily be followed by the cytological changes. In conclusion, vincristine was found to be effective chemotherapeutic agent.

The effect of vincristine treatment on semen parameters in a male boxer with a genital transmissible venereal tumour are described. The dog was treated with vincristine intravenously at 0.5 to 0.7 mg/m2 body surface area per week for six weeks until complete regression of the tumour occurred. Semen samples were collected before each application and then at weeks 10, 12, 17, 21 and 23 after the start of therapy. There were no alterations in libido or in testicular size and consistency either during or after treatment. Total sperm count decreased to abnormally low values during weeks 4 and 5, and then began to increase up to pretreatment values. No significant alterations in the other semen parameters were found during the study period.

The medical records of six dogs with primary intranasal transmissible venereal tumour (TVT) were reviewed. Epistaxis (4/6), serosangineous nasal discharge (2/6), oronasal fistulae (2/6), facial swelling (1/6) and submandibular lymphadenopathy (3/6) due to reactive hyperplasia (2/3) and metastasis (1/3) were the most common complaints and clinical findings. Diagnosis was made by rhinoscopy and confirmed by cytology and histopathology in five dogs and by cytology only in one dog. The microscopic appearance of the tumours with both diagnostic techniques was typical of TVT. Four cases were treated effectively with four to five weekly cycles of vincristine monotherapy that resulted in complete resolution of TVT masses in approximately 1 month. One case was resistant to this kind of treatment and another one was lost to follow-up.

Eleven dogs with canine transmissible venereal tumour (CTVT) were given vincristine sulphate chemotherapy to induce tumour regression. Biopsy specimens were collected from tumours during the growth phase, before chemotherapy, and again from the same dogs during the regression induced by chemotherapy. Laboratory assessment included cytology, histology, the number of tumour cells in relation to the number of intratumoral leucocytes, proliferative and apoptotic fractions of tumour cells, intratumoral vessel density, and fibrosis. The results revealed that during regression, tumour cell proliferation ceased, apoptosis increased, leucocytes increased (with increased proportion of T lymphocytes), tumour parenchyma collapsed around intratumoral vessels, and fibrosis increased. These results, which were similar to findings in dogs with spontaneous regression of CTVT, suggest that tumour immunity plays a role in tumour regression after modest chemotherapy., (Copyright 2000 Harcourt Publishers Ltd.)

A five-year-old crossbred dog was referred with rapidly growing masses over its penis and right popliteal lymph node. The dog had severe blepharospasm, congestion of episcleral vessels and rubeosis iridis of the left eye. A presumptive diagnosis of transmissible venereal tumour (TVT) and iridocyclitis was made based on the results of fine needle aspiration. Chemotherapy with vincristine and prednisolone was initiated and after four months the dog made a complete recovery. However, the dog subsequently relapsed, showing miosis, blepharospasm and a well defined mass within the anterior chamber of the left eye. In addition, the dog exhibited generalised 'grand mal' type seizures. Computed tomographic (CT) examination of the brain revealed two distinct masses in the left frontal lobe. Because of the poor prognosis, the owners elected to have the dog euthanased. On histopathology, metastases of TVT in the left eye and left cerebral hemisphere were found, showing no specific staining for CD3, immunoglobulin (Ig) G, IgM and lambda light chains. It was therefore concluded that the tumour growth was progressive, and that there was an absence of local humoral immune response against TVT in this case.

The aim of this study was to evaluate the direct effects of vincristine on semen quality in dogs with transmissible venereal tumor (TVT). We examined the semen of 17 dogs suffering from TVT during vincristine treatment. Each animal received 0.6 mg, i.v. vincristine sulphate per square meter of body surface, per week for 4 wk until complete regression of the tumor. The following semen parameters were evaluated: semen volume (second fraction), sperm concentration, total spermatozoa per ejaculate, percentage of progressively motile spermatozoa, percentage of dead spermatozoa, percentage of swollen spermatozoa (hypo-osmotic swelling test) and percentage of morphologically abnormal spermatozoa (primary and secondary defects). Semen was collected and evaluated prior to the beginning of treatment, 3 d after each vincristine injection and 15 d after the last injection. Semen characteristics transiently deteriorated during treatment, but returned to normal 15 d later. These changes were attributed to a direct effect of vincristine on the extragonadal spermatozoal reserves contained in the epididymis and ductus deferens. A GnRH stimulation test was also performed after each semen collection in order to assess the function of the hypothalamic-pituitary-Leydig cell axis. No effect was noted on the above axis.

Mice with a severe metastasized tumour burden can be cured with a single local injection of interleukin-2. Such a treatment can also be effective against ocular squamous cell carcinoma in cows and transmissible venereal tumours in dogs. We did not notice any toxic effects of this treatment.

Twenty-nine cases of naturally occurring, transmissible venereal tumor were studied retrospectively. The external genitalia was the primary site of tumor involvement in 27 dogs, with the remaining two dogs having primary intranasal involvement. Extragenital tumor involvement was identified in six cases, including five cases with metastatic disease. Fifteen cases were treated effectively with radiation therapy alone. Radiation therapy also was effective in four cases that were resistant to chemotherapy. Four of five cases treated with at least four doses of vincristine as a solitary agent also achieved complete remissions. Transmissible venereal tumor remains a unique canine tumor that often is curable despite the development of extragenital primary lesions or metastasis.

Ten canine transmissible venereal tumour (TVT) cases were studied by digital image analysis quantification on sections stained with silver to demonstrate nucleolar organizer regions (Ag-NORs). In each animal, 100 neoplastic cells were randomly selected for evaluation. The following parameters were measured or calculated: area of nucleus, area of Ag-NOR dot, the mean number of Ag-NOR dots per nucleus, the mean area of Ag-NOR dots per nucleus and the ratio of mean nuclear dot area to nuclear area. All 10 cases were treated with vincristine at a dose of 0.6 mg/m2 intravenously once a week. Two, which showed malignant characteristics (i.e. uncontrolled growth, local invasion or metastasis), did not respond to multiple (12) treatments and had a fatal outcome. Of the remaining eight cases, seven responded to two to six treatments and one required 12 treatments. The average number of Ag-NORs per nucleus and the area of Ag-NORs per nucleus were lower in the seven cases that responded to two to six treatments than in the other three cases, but the difference was not significant. However, there was a significant difference in the ratios of Ag-NOR area to nuclear area between the two groups of cases. Thus, poor prognosis was (1) possibly correlated with an increase in the mean number of Ag-NORs per nucleus and an increase in the mean area of Ag-NORs per nucleus, and (2) definitely correlated with an increase in the mean ratio of Ag-NOR area to nuclear area.

During a 21-month period, 48 dogs with spontaneous canine transmissible venereal tumor (clinical stage, T1-T3) were presented to the Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria, and were divided into one control and four treatment groups to test the efficacy of single-agent chemotherapeutic drugs. The dogs were not randomly assigned to groups because each chemotherapeutic agent was not continuously available during the test period. Group I consisted of four dogs that received oral cyclophosphamide (50 mg/M2 body surface area [BSA]) on the first four days for six weeks. No therapeutic response was noted in any of the four dogs. Group II consisted of ten dogs that received intravenous (IV) cyclophosphamide (50 mg/M2 BSA) for four consecutive days per week for six weeks. Two of the ten had a partial remission. Group III consisted of eight dogs that received oral methotrexate (2.5 mg/M2 BSA) every other day for six weeks. No therapeutic response was noted in any of the eight dogs. Group IV consisted of 20 dogs that were administered IV vincristine sulfate (0.5 mg/M2 BSA) weekly until a response was noted. Complete remission occurred in each of the 20 dogs. One dog had recurrence within 12 months. Group V was the untreated control group, consisting of six dogs among which no spontaneous remission was seen. Instead, tumor progression was noted. Adverse responses to medication, anorexia, vomiting, diarrhea, and weight loss were seen only with dogs treated with cyclophosphamide and methotrexate.

Thirty dogs with transmissible venereal tumors were examined either at The Donaldson-Atwood Cancer Clinic of The Animal Medical Center or at The University of Georgia Veterinary Medical Teaching Hospital. After biopsy, all dogs were treated with a combination chemotherapy regimen consisting of vincristine, cyclophosphamide, and methotrexate. Results of therapy were evaluated after a mean interval of 533 days; 28 had complete regression of tumor, 1 had a partial response, and 1 had a minimal response.

Administration of the vasodilator hydralazine to a single mongrel dog with a transplanted, superficial transmissible venereal tumour in the abdomen permitted tumour-adjacent normal tissue temperature differences produced in local hyperthermia to be enhanced by nearly 2 degrees C. A preliminary study of tumour and normal tissue perfusion rate in the dog, employing the 15O-labelled water-positron emission tomography technique, suggested that administration of the vasodilator led to a significant reduction in the tumour perfusion rate, consistent with the observed tumour temperature enhancement. Computational studies with a multi-layer, one-dimensional cylindrical model of deep-tumour heating suggest that vasodilator-induced reductions of tumour perfusion rates could significantly increase deep tumour-superficial normal tissue temperature differences produced in deep-tumour thermotherapy.

The present study was undertaken to evaluate infusion of cryopreserved autologous bone marrow following supralethal chemotherapy in canines bearing a solid tumor thought to be moderately sensitive to cytotoxic agents. Initial studies in 5 dogs established a combination of busulfan (Bu) 3 mg/kg X 2 days and cyclophosphamide (Cy) 50 mg/kg on day 3 to produce bone marrow lethality within 14 days (high dose regime). Bu 1 mg/kg, Cy 20 mg/kg produced tolerable toxicity (low dose regime). Eight pairs of dogs were challenged with 3 X 10(8) transmissible venereal tumor cells. Measurable progressive tumor growth occurred in all instances. Marrow aspirated from the femoral shafts of the animals was cryopreserved in 10% DMSO. One dog of each pair received the high dose Bu + Cy regime followed in 30 h by marrow infusion and his partner received the low dose regime without marrow. Tumors were measured serially for at least 2 months. Infusion of marrow resulted in evidence of hematologic recovery within 2 weeks following the high dose regime. Tumor responses occurred in both groups when compared to 8 untreated tumor challenged controls. High dose animals had greater initial responses than low dosed dogs but long term responses were not significantly different. Eight dogs rechallenged with tumor cells after initial successful therapy failed to develop tumors. It was concluded that: a) cryopreserved autologous bone marrow infusion was effective in protecting tumor bearing canines from otherwise lethal chemotherapy; b) the transmissible venereal tumor of canines responded to both high and low dose regimes; c) the rescue of dogs by stored autologous marrow did not offer additional benefits in tumor control over a standard regime; d) chemotherapy treated dogs resisted tumor rechallenge. This model may offer a large animal system to study the autologous marrow rescue concept during controlled periods of tumor evolution.