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Background: The most common first-line treatment for canine lymphoma is a chemotherapy protocol that includes cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Canine high-grade T-cell lymphoma has been found to have a significantly poorer prognosis than high grade B-cell lymphoma. Several studies have investigated alternative protocols for non-indolent T-cell lymphoma. This retrospective study investigated using a cyclophosphamide, lomustine, vincristine, and prednisone protocol (CLOP) for naïve non-indolent T-cell lymphoma patients. Methods: In this retrospective study, medical records of dogs treated for non-indolent T-cell lymphoma at a veterinary teaching hospital from 2017 to 2022 were reviewed. Response rate, toxicity, progression-free survival and survival time were calculated. Factors potentially related to prognosis were statistically analyzed. Results: Twenty-six dogs were included in the study. The median progression-free survival (PFS) time was 166 days (95% CI 119–213). The median overall survival time (OST) for the whole study group was 318 days (95% CI 239–374). Twenty-four dogs experienced gastrointestinal adverse events during the protocol, with 79% of them being grade 1 or 2 as per VCOG-CTCAE v2. Conclusions: This protocol has shown similar median PFS time and OST compared with previous studies for canine non-indolent T-cell lymphoma treated with CHOP, along with minimal toxicity, and suggests the inclusion of lomustine in first-line chemotherapy protocol against canine non-indolent T-cell lymphoma may be beneficial. [ABSTRACT FROM AUTHOR]

Background: Transmissible venereal tumour (TVT), also called Sticker Tumour, is a round cell tumour whose transmission occurs mainly through sexual contact between animals or direct transplantation of the neoplastic cell through licking or through direct contact with the lesioned area. TVT is the most common tumor found in stray dogs and predominantly affects the genital area and, in case of bitches, occurs in the vagina and foreskin, as well as the oral and nasal cavities. Intracavitary TVT is rarely reported. The aim of this paper is to report a case of an old neutered bitch affected by vaginal and intracavitary TVT, treated at the Veterinary School Clinic (CVE) of the Federal University of Santa Catarina (UFSC), Curitibanos campus, Brazil. Case: An approximately 10-year-old mixed breed bitch, weighing 18,5 kg and, neutered 2 years previously at the same institution, was brought by her owner, who reported dyskinesia, constipation, and serosanguinous vaginal discharge for a few weeks. Physical examination showed a row of 4 smooth, round masses with a soft consistency ranging from 1 to 2 cm at the bottom of the vaginal roof. The patient was referred for an ultrasound (US) and a vaginal swab was taken for cytological examination, whose result demonstrated TVT. The result of the US scan showed a heterogeneously shaped structure, with a more hypoechogenic center in relation to the periphery and irregular contours, measuring around 2.63 x 6.10 cm, in the uterine topography caudally to the bladder. Exploratory laparotomy was performed with total removal of the mass, which was surrounding the proximal urethra, and the material was sent for histological and cytological analysis, whose both results indicated TVT. Chemotherapy was then initiated, with 6 intravenous administrations of vincristine (0.5 mg/m2) with an interval of 15 days between each administration. The animal underwent a total of 6 chemotherapy sessions, without complete improvement of the vaginal tumours. A 2nd chemotherapy protocol based on doxorubicin was suggested, which was not accepted by the owner. Three months after the end of the original chemotherapy protocol, the patient was assessed again and it was found that there had been no progression of the vaginal masses on vaginal palpation and no signs of recurrence of the intracavitary mass on ultrasound. Discussion: TVT is a venereal tumor that affects almost 100% of non-neutered animals, males and females. In the case of bitches, the most common sites are the vagina (53%), vulva (13%) and extragenital areas (14%). This animal had no intracavitary mass at the time of her castration 2 years earlier. At the time of diagnosis, she had the extragenital form of the tumor, consisting of an intra-abdominal mass, in addition to the genital masses in the vaginal roof. The chemotherapy drug vincristine is the drug of choice for the treatment of transmissible venereal tumors, due to its high efficacy associated with 4 to 6 sessions. However, in this case, there was no total improvement, so it was classified as a case of proven pharmacological resistance as the chemotherapy was ineffective for the complete regression of the tumor. It was therefore concluded that the occurrence of intracavitary TVTs, although rare, warrants a thorough physical examination combined with diagnostic tools such as ultrasound and histology, even in castrated old patients. [ABSTRACT FROM AUTHOR]

Background: The Transmissible Venereal Tumour (TVT) is a round cell neoplasm that affects dogs. Its localisation is predominantly venereal; however, it can be found in extragenital regions, such as skin, nostrils, mouth and eyes. This paper describes a case of nasal TVT in a geriatric dog, performing its clinical, laboratory, therapeutic and prognostic analysis. Case: A 13-year-old male dog, mixed breed, non-castrated, domiciled, weighing 19,200 kg, was attended at the Small Animal Medical Clinic (CMPA) of the University Veterinary Hospital (HVU) of the Multidisciplinary Centre of the Barra Campus, Federal University of Western Bahia (UFOB), presenting cachexia, reactive lymph nodes except the popliteal ones, dehydration, dyspnoea, arrhythmia, frequent sneezing with serous and yellowish nasal discharge, cough, difficulty in breathing, increased volume in the face (left nasal plane), enlarged volume above the right eye with a suppurative wound just below. The animal's haemogram revealed the presence of normocytic normochromic anaemia, neutrophilic leukocytosis with left regenerative shift and hyperproteinaemia. The serum biochemical tests for renal function (urea and creatinine) and hepatic function (ALT, AST and AF) showed normal levels. The cytological evaluation showed a monomorphic population of large cells with a round nucleus, condensed chromatin and 1 to 2 prominent nucleoli, abundant and slightly basophilic cytoplasm, with multiple punctuated vacuoles, showing discrete anisocytosis and anisokaryosis and mitotic figures, confirming a case of TVT. In addition, the presence of neutrophils was evidenced, indicating an inflammatory process. Simultaneously, an X-ray of the skull was requested, which was not returned. A chemotherapy protocol was instituted using vincristine sulphate [0.025 mg/kg IV], for 5 sessions with an interval of 1 week between each session, clinical and laboratory monitoring of the regression of neoplastic cells, demonstrating total efficacy. It is worth noting that after the 2nd application of the pharmaceutical, the animal presented adverse reactions, with clinical symptoms of emesis, decreased appetite and weight loss; so, the animal was then subjected to fluid therapy, treatment with immunostimulants, appetite stimulants and antiemetics, which influenced its clinical improvement. Discussion: The importance of complementary diagnostic tests in the routine of veterinary clinics and hospitals is noticeable, aimed at establishing the diagnosis and therapeutic monitoring of diseases. In the present report, diverging from the majority of cases described in the literature, the animal showed signs of neoplasia at 13 years of age, in a context of reduced sexual activity. It is believed that the fact that he has free access to the street and has olfactory habits inherent to the canine species in terms of contact with the genital region of other animals, left him exposed to factors that determined the transmissibility of the neoplasm. Weekly clinical follow-up as well as laboratory tests, was essential to ascertain the effectiveness of the treatment, the presence of adverse reactions and the introduction of new drugs. The normocytic normochromic anaemia possibly occurred in response to the nodular and haemorrhagic characteristics of the tumour tissue. The leukocytosis due to neutrophilia and hyperproteinaemia would be related to the occurrence of an acute infectious process, probably bacterial. It is concluded that although geriatric patients present immunosuppression more easily than other age groups, in cases of TVT, the therapeutic approach with vincristine sulphate, and the clinical and laboratory follow-up adopted influence the good prognosis concerning neoplastic regression. [ABSTRACT FROM AUTHOR]

Primary intranasal transmissible venereal tumor is an uncommon manifestation of venereal tumor in sexually intact dogs. A two-year-old male non-descript dog was presented with a history of abnormal unilateral nasal swelling, sneezing, recurrent epistaxis, and unilateral mucohaemorrhagic nasal discharge for the past three weeks. During clinical examination, numerous friable masses attaching to the gums and infiltrating the nasal septum on the right side were observed. The skull radiograph revealed increased soft tissue density in the nasal cavity with osteolysis of the maxillary bone. Cytological examination of the mass revealed numerous neoplastic round cell populations with low-to-moderate anisocytosis, anisokaryosis, a prominent mitotic figure, and abundant faint basophilic cytoplasm with unique punctate cytoplasmic vacuoles suggestive of nasal form of transmissible venereal tumor (TVT). The dog was treated with vincristine sulphate at a dose rate of 0.025 mg/kg BW intravenously once weekly for a total of five doses, along with other supportive therapies After the second dose of vincristine therapy, the clinical signs continued to improve, and the dog achieved a smooth and uneventful recovery after completing five doses of vincristine therapy. [ABSTRACT FROM AUTHOR]

Copyright of Harran University Journal of the Faculty of Veterinary Medicine / Harran Üniversitesi Veteriner Fakültesi Dergisi is the property of Harran University, Faculty of Veterinary Medicine 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.)

Copyright of Canadian Journal of Veterinary Research / Revue Canadienne de Recherche Vétérinaire is the property of Canadian Veterinary Medical Association 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.)

Copyright of Canadian Journal of Veterinary Research / Revue Canadienne de Recherche Vétérinaire is the property of Canadian Veterinary Medical Association 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.)

Lymphoma is a malignant tumor commonly diagnosed in dogs representing 7-24% of all canine tumors. There has been no previous studies focused on characterization of canine lymphoma cases in Latvia. The goals of this retrospective study were to determine prevalence and characteristics of lymphoma cases among biopsy submissions to a private veterinary pathology service that receives approximately 80% of all biopsy submission in Latvia and to compare this data with published canine lymphoma reviews. Data were retrieved to select records from Latvian dogs diagnosed with lymphoma between 2011 and 2020, determining characteristics of dogs and types of lymphoma based on anatomic distribution and cellular morphology. In a ten-year study period, diagnosis of lymphoma constituted 1-4% of surgical biopsy submissions each year without upwards trend. Affected dogs were middle age (median 8 years; range 2-13), with a slight male predominance (58%). The majority of dogs (19%) were mixed breed. Top 3 affected dog breeds were Rottweiler, American Staffordshire terrier and French bulldog with 6-7 cases in each breed. Multicentric form of lymphoma predominated (55%) followed by alimentary and mucocutaneous lymphoma (21% and 14%, respectively). Within multicentric form of lymphoma two thirds were intermediate to large cell lymphomas. Included in this group would be diffuse large B cell lymphomas, the most common subtype of canine lymphomas; however, lack of immunohistochemical testing precluded complete lymphoma classification according to WHO guidelines. Results of this study correlate well with the previously published results and provide important information to Latvian small animal veterinarians and pathologists. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment is an important target of studies in different types of neoplasms. Understanding the role of general components such as immune, vascular and fibroblastic cells has the objective of contributing to prognosis and treatment. The aim of this study was to evaluate the relationship between mast cells and angiogenesis in benign and malignant mammary neoplasms by investigating the role of degranulation and microlocation of mast cells and neoformed vessels in canine mammary neoplasms. Materials, Methods & Results: Mammary glands (n = 122) from 50 female dogs submitted to mastectomy without chemotherapy were evaluated and categorized into 3 groups: control group (n = 46); malignant group (n = 57) and benign group (n = 19). Lymph nodes without changes (n = 59) and with metastases (n = 6) were also evaluated. To evaluate the MCD (mast cell density) and angiogenesis, Toluidine Blue (0.1%) and Gomori’s Trichrome techniques were performed and adapted from previous studies. Photomicrographs of 10 hotspot areas on a 40x objective lens of the mammary glands and lymph nodes were captured to assess MCD and angiogenesis. In the absence of these areas, random fields were captured. For the mammary glands of the malignant and benign groups, 20 fields were analyzed, as the analysis considered the microlocation (peritumoral and intratumoral). Counting was performed manually using ImageJ software version 1.42q by 2 observers. The statistical analysis were performed using SPSS software version 19.0. The most frequent histological type in the malignant group was carcinoma in mixed tumor (68.42%; 39/57) and in the benign group was benign mixed tumor (57.89%; 11/19). Female dogs without breed pattern were more frequently affected represented 70% of the animals and the mean age was 9 years and 8 months ± 3 years and 1 month. The granulated density of mast cells and peritumor vessels was higher in the malignant group (P = 0.03; P = 0.02). There was also a positive correlation between intratumor and total vessel density and mast cell density. There was no significance between the malignant and benign groups in regard with fibrosis density. Discussion: In this study were observed a greater density of blood vessels in malignant group, suggesting the participation of blood vessels for neoplastic proliferation. Furthermore, these vessels were located in the peritumoral region as in previous studies. The positive correlation between MCD and blood vessels was similar to a previous study performed in canine breast carcinomas and breast cancer in women. Regarding microlocation, another study also found higher MCD in the peritumoral region than in the intratumoral region of canine carcinomas. Although there are already studies for this purpose in cases of oral squamous cell carcinoma in humans, we believe this is the first study to investigate the role of mast cell degranulation in mammary neoplasm of bitches. The MCD was not significant among the malignant and benign groups and in the mammary glands of the control group the MCD was higher, as observed by other studies. Future studies should be associated the survival time and the presence of metastases in order to confirm the findings. In view of these findings, we may conclude that a higher density of mast cells is related to a higher density of blood vessels and that these are more abundant in malignant neoplasms, which reinforces the crucial role of angiogenesis in the neoplastic development. [ABSTRACT FROM AUTHOR]

First-line treatments of cancer do not always work, and even when they do, they cure the disease at unequal rates mostly owing to biological and clinical heterogeneity across patients. Accurate prediction of clinical outcome and survival following the treatment can support and expedite the process of comparing alternative treatments. We describe the methodology to dynamically determine remission probabilities for individual patients, as well as their prospects of progressionfree survival (PFS). The proposed methodology utilizes the ex vivo drug sensitivity of cancer cells, their immunophenotyping results, and patient information, such as age and breed, in training machine learning (ML) models, as well as the Cox hazards model to predict the probability of clinical remission (CR) or relapse across time for a given patient. We applied the methodology using the three types of data obtained from 242 canine lymphoma patients treated by (L)-CHOP chemotherapy. The results demonstrate substantial enhancement in the predictive accuracy of the ML models by utilizing features from all the three types of data. They also highlight superior performance and utility in predicting survival compared to the conventional stratification method. We believe that the proposed methodology can contribute to improving and personalizing the care of cancer patients. [ABSTRACT FROM AUTHOR]

A 7‐year‐old, intact, female Jack Russell terrier was presented for evaluation of a mammary nodule. Abdominal ultrasonography for initial staging revealed a 1 cm hypoechoic nodule within the left lateral hepatic lobe (LLHL), which was histologically determined to be a plasma cell tumour (PCT). Computed tomography revealed an additional 5 mm nodule in the right medial hepatic lobe (RMHL). Exploratory celiotomy showed that the PCT in the LLHL adhered to the gastric wall. Partial liver lobectomy and partial gastrectomy were carried out to remove the PCT in the LLHL. Marginal excision was done to remove the RMHL nodule, which was determined to be a PCT. The dog was treated with prednisone and melphalan for 6 months and remained in complete clinical remission for 37 months. Surgery and adjuvant chemotherapy were successful in maintaining long‐term remission in this patient. This is the first report of primary multicentric hepatic PCT in a dog. [ABSTRACT FROM AUTHOR]

Copyright of Veterinarska Stanica is the property of Croatian Veterinary Institute 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.)

The etiology of dilation of lymphatic vessels, termed as intestinal lymphangiectasia, remains unknown. In most cases, it occurs secondary to other pathologic conditions such as gastrointestinal neoplasms. However, only a few cases of canine intestinal lymphangiectasia concurrent with non-gastrointestinal neoplasms have been reported so far. Moreover, the correlation between intestinal lymphangiectasia and non- gastrointestinal neoplasms has not been discussed in any other literature. In this study, we report a rare case of intestinal lymphangiectasia concomitant with renal cell carcinoma in an 11 year old female mixed Maltese, suggesting that non-gastrointestinal neoplasms could be associated with the development of intestinal lymphangiectasia. On gross observation, the small intestine was irregularly swollen presenting an accordion like shape. Microscopic examination revealed prominent dilatation of the lymphatic vessels, especially, within the submucosa and muscularis layer. The lacteals within the villi were dilated and presented "club-shaped" tips. The carcinoma might trigger intestinal lymphangiectasia by compressing the main lymphatic vessels or the cisterna chyli, subsequently increasing the pressure of the lymphatic vessels in the gastrointestinal tract. Moreover, metastasis of the carcinoma to the gastrointestinal tract could induce intestinal lymphangiectasia. Thus, the occurrence of intestinal lymphangiectasia must be considered when an abdominal neoplasm is located around major lymphatic vessels. [ABSTRACT FROM AUTHOR]

Precise diagnosis and prognosis are key in prevention and reduction of morbidity and mortality in all types of cancers. Here we show that changes in the collagen fibres in the main histological subtypes of canine mammary gland carcinomas are directly associated with the tumour behaviour and the animal survival time and could become a useful tool in helping with diagnosis. Imaging by second harmonic generation and multiphoton excited fluorescence microscopy were performed to evaluate the collagen and cellular segment parameters in cancer biopsies. We present a retrospective study of 45 cases of canine mammary cancer analysing 836 biopsies regions including normal mammary gland tissue, benign mixed tumours, carcinoma in mixed tumour, carcinosarcoma, micropapillary carcinoma and solid carcinoma. The image analyses and the comparison between the tumour types allowed to assess the collagen fibre changes during tumour progression. We demonstrate that the collagen parameters correlate with the clinical and pathological data, the results show that in neoplastic tissues, the collagen fibres are more aligned and shorter as compared to the normal tissues. There is a clear association of the mean fibre length with the dogs survival times, the carcinomas presenting shorter collagen fibres indicate a worse survival rate. [ABSTRACT FROM AUTHOR]

Immunotherapy targeting programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1) represents promising treatments for human cancers. Our previous studies demonstrated PD-L1 overexpression in some canine cancers, and suggested the therapeutic potential of a canine chimeric anti-PD-L1 monoclonal antibody (c4G12). However, such evidence is scarce, limiting the clinical application in dogs. In the present report, canine PD-L1 expression was assessed in various cancer types, using a new anti-PD-L1 mAb, 6C11-3A11, and the safety and efficacy of c4G12 were explored in 29 dogs with pulmonary metastatic oral malignant melanoma (OMM). PD-L1 expression was detected in most canine malignant cancers including OMM, and survival was significantly longer in the c4G12 treatment group (median 143 days) when compared to a historical control group (n = 15, median 54 days). In dogs with measurable disease (n = 13), one dog (7.7%) experienced a complete response. Treatment-related adverse events of any grade were observed in 15 dogs (51.7%). Here we show that PD-L1 is a promising target for cancer immunotherapy in dogs, and dogs could be a useful large animal model for human cancer research. [ABSTRACT FROM AUTHOR]

Background/Aim: Periostin (POSTN) has a significant role in proliferation and migration of tumour cells as well as tumour progression. This study aimed to determinate POSTN expression in cancer cells in malignant and benign tumours of the mammary gland in female dogs. Materials and Methods: All together 83 cancers, 24 adenomas and 7 unchanged fragments of the mammary glands of bitches were investigated. Immunohistochemistry was performed using anti-POSTN, Ki-67 and HER2 antibodies. Results: POSTN expression was observed in cancer cells in 31.3% of malignancies and 12.5% of benign tumours. A significantly positive correlation between expression of POSTN in cancer cells and the degree of histological malignancy, expression of Ki-67 antigen and expression of POSTN in CAFs was found. Conclusion: The obtained results suggest the possible participation of POSTN in the process of carcinogenesis and progression of mammary tumors in bitches. [ABSTRACT FROM AUTHOR]

Evidence is accumulating that tumour development is driven by cancer stem cells (CSCs). In order to understand the presence and potential contribution of stem cells (SCs) as tumour-initiating cells in canine cutaneous tumours, we selected three putative SC markers (Lgr5, Lgr6 and Sox9) and investigated their expression pattern, level of protein and mRNA expression, in 43 canine hair follicle (HF) and 18 canine cutaneous epidermal tumours by immunohistochemistry and qRT-PCR, using normal skin samples as controls. Lgr5 protein expression was not detected in epidermal and HF tumours; however, Lgr5 mRNA overexpression was evident in some HF tumours. Sox9 was expressed in several tumour cases, both at the protein and mRNA level. The Lgr6 antibody tested was not suitable for formalin-fixed paraffin-embedded tissue samples, but Lgr6 gene showed higher expression in several samples of both HF and epidermal tumours compared with normal skin. Significantly higher mRNA expression levels of the three SC markers were found in trichoblastomas (TB) compared with basal cell carcinomas (BCC). The present results indicated that canine HF and epidermal tumours might have common tumour-initiating cells. The mRNA expression of the three selected SC markers, especially Lgr5, could be potentially useful in the distinction between canine TB and BCC. [ABSTRACT FROM AUTHOR]

Parameters of 37 canine mammary malignant tumors and 13 dysplasia were compared. The age of an animal at the time of treatment in veterinary clinic, the age of the first factors of neoplasm, the number of births during life and the period of the last one, feeding nature, pseudo pregnancy and lactation cases, the number and location of affected mammary gland, neoplasm macro characteristics were considered. The size of the letter was determined with a view to three factors, the occurrence of capsules in neoplasms was ranked in points. The intensity of lactation malfunction was determined under the same method. Canine mammary dysplasia was examined at an earlier age than malignant tumors. This is partly due to the earlier onset than in the case of malignant tumors. At the same time, period between cancer discovery and treatment in the latter case was much shorter. It may state faster growth of tumors in case of malignancy than in mammary dysplasia. A significant difference in neoplasms size - malignant tumor and dysplasia is the proof thereof. Study of the influence of the number of births in the occurrence of different mammary neoplasms showed that dogs with dysplasia gave birth twice as less than those with diagnosed malignant tumors. The period between the last birth and identification of factors of disease for both groups of animals was the same. There was no significant difference also in the frequency of cases with lactation malfunction in dogs with mammary malignant tumors and dysplasia. Groups of animals with mammary malignant tumors and dysplasia differed on such characteristics as frequency of tumors with full, partial or no capsule, and the average number of mammary gland affected and their localization. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) area‐under‐the‐curve (AUC) was calculated for 40 dogs with spontaneously occurring cancers using a previously validated limited‐sampling approach. All dogs were administered a dose of 30 mg/m2 by intravenous infusion and serum samples were collected at 5, 45 and 60 minutes post‐infusion. DOX and its major metabolite, doxorubicinol (doxol), were quantified in serum samples using high‐performance liquid chromatography tandem‐mass spectrometry. Wide interpatient variability was observed in the predicted DOX AUC with a coefficient of variation of 34%. A significant relationship was found between DOX AUC and absolute white blood cell count (P = 0.003), absolute neutrophil count (ANC; P = 0.002) and surviving fraction of neutrophils (P = 0.03) approximately 1 week after dosing (nadir). No changes in other hematologic parameters (red blood cells, platelets, lymphocytes, haemoglobin) were found to correlate with DOX AUC. The absolute dose (mg) and the dose per unit body weight (mg/kg) were not significantly correlated with nadir ANC. No relationships were found between maximum serum doxol concentration and myelosuppression. Baseline ANC was also significantly correlated to nadir ANC and a model was constructed using baseline ANC and DOX AUC that significantly described the nadir ANC. These findings demonstrate the important relationship between systemic DOX exposure and degree of neutropenia in dogs, and suggest a potential for individualized, pharmacokinetically‐guided DOX dosing in dogs. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is a frequently recognized dermal tumour in dogs and has been described as a common pathology induced by solar ultraviolet radiation exposure. Little has been published about this neoplasm with regard to clinical features and outcome in dogs. This retrospective study included 193 dogs from a single institution histopathologically diagnosed with SCC of the dermis. Thirty‐eight percent of all dogs had documented histopathologic actinic change. The overall median survival time was 1004 days, with the population demonstrating actinic change associated with a significantly longer survival time (median 1359 days, range 16‐3530 days) compared to dogs without actinic change (median 680 days, range 16‐3066 days) and this achieved significance on multivariate analysis (hazard ratio 0.42, 95% confidence interval 0.193‐0.930, P = 0.032). These data demonstrate increased survival of dogs with SCC demonstrating actinic change over those with non‐actinic SCCs, and purports long‐term survival for these animals. Dogs received a variety of treatment approaches as a retrospective study, and future prospective studies will be necessary to investigate whether adjunct therapies such as radiation or chemotherapy offer improvement in survival for dermal SCC in the dog. [ABSTRACT FROM AUTHOR]

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. [ABSTRACT FROM AUTHOR]

Highlights • The results showed similar epidemiologic features for human and canine non-Hodgkin's lymphoma (NHL). • Human and canine age-standardised risk (ASR) were significantly correlated (r = 0.664, P < 0.05). • The highest values for human and canine risks were detected in urban areas of Greater Porto. Abstract Lymphoma is one of the most common neoplasms in dogs and it is one of the top five causes of cancer-related deaths, similar to human lymphoma. Companion animal epidemiological studies define dogs as sentinels of potential risk factors for human health, mainly due to shared environments, shorter disease latencies, and spontaneous disease. The aims of this study were to describe human and canine epidemiologic features of non-Hodgkin's lymphoma (NHL) and their similarities, and to investigate a possible geographical association in the incidence risks in the Greater Porto area, in north-western Portugal. The postal codes of human NHL patients diagnosed between 2005 and 2010 residing in the Greater Porto, Portugal, were obtained from North and Central Region Cancer Registries of Portugal. Available data from dogs diagnosed with lymphoma between 2005 and 2016 from several veterinary centres were also collected. Descriptive epidemiology, mapping cases, and age-standardised risks of NHL incidence (ASR) were determined for both species. The results showed a higher risk (P < 0.05) of NHL in men (ASR men: 18.1 cases/100,000 inhabitants; women: 14.2 cases/100,000 inhabitants) and in male dogs (ASR males: 82 cases/100,000 dogs; females: 70 cases/100,000 dogs). The geographical distribution of human and canine ASR was well correlated (r = 0.664, P < 0.05), with the highest values for human and canine ASR detected in the same urban municipalities of the Greater Porto: Porto, Matosinhos and Maia. These findings suggest the existence of exposure similarities, supporting the relevance of cancer surveillance in pet animals as efficient tools to predict health hazards for humans. [ABSTRACT FROM AUTHOR]

In female dogs, mammary tumors are the most common neoplasia representing about 50% of the tumors affecting this species. In women, the importance of mutations in BRCA1 and mammary tumors development is well established. However, little information is available on the molecular mechanisms that contribute to canine mammary tumors. In this work, we evaluated the mutational and methylation status of the BRCA1 gene, in tumoral and non-tumoral tissues of canine mammary glands in order to characterize its influence in mammary carcinogenesis on this species. Samples of 16 animals were collected and two hotspot regions (intron 8-exon 9 and 5′UTR) were sequenced. For methylation analysis, the bisulfite sequencing PCR approach was used. No evidence of hypermethylation was observed in the BRCA1 promoter region, suggesting this mechanism may not be involved in BRCA1 silencing in canine mammary tumorigenesis. No alteration was observed in intron 8-exon 9 region. On the other hand, two polymorphisms in the 5′UTR region were observed: a transition (T > C) that has not been previously described in the literature, and observed in one patient with an unfavorable prognosis, and the previously described transversion (C > G). We suggest that methylation is not the main BRCA1 inactivation mechanism in sporadic CMTs. Regarding the genetic alterations, two variations were detected in our population, and we were able to detect regional allele frequency differences in our population. [ABSTRACT FROM AUTHOR]

Spontaneous tumors arising from mammary tissue are considered the most common tumor in female dogs and are of great importance both in veterinary and comparative medicine. Interleukin-15 is a cytokine involved in many physiologic processes such as activation of immune cells, autoimmune diseases, and cancer pathogenesis; however, the role of interleukin-15 in canine mammary cancers has not been well understood. We designed this study to examine the expression of interleukin-15 (IL-15) in canine mammary carcinoma by means of immunohistochemistry and any possible association with histologic malignancy grades, Bcl-2 expression, tumor recurrence, and overall survival. Results revealed that 14 (46.66%) of tumor samples strongly express IL-15, 7 cases (23.33%) moderately, and 9 cases showed weak immunoreactivity (30%). The expression of interleukin-15 is increased in canine mammary tumors in comparison to healthy tissues (p < 0.05). Additionally, interleukin-15 higher expression is significantly in relationship with high histologic grade (p < 0.05), high Bcl-2 expression (p < 0.05), and shorter overall survival (p < 0.05), but not with tumor recurrence (p > 0.05). Interleukin-15 could have a role mammary carcinogenesis in dogs but more studies are needed to understand its exact roles. [ABSTRACT FROM AUTHOR]

The balance between pro‐ and anti‐angiogenic signalling is tightly regulated in normal tissues to maintain the functions of the vasculature. In contrast, the overproduction of angiogenic factors and enhanced angiogenesis are frequently observed in several types of tumours. Although there have been many reports on the correlation between tumour progression and angiogenesis in humans, little is known about tumour angiogenesis in canines. Hence, we attempted to clarify whether angiogenesis contributes to tumour progression in canines as well as humans. In this study, we investigated the expression of several angiogenesis‐related genes, including CD34,VEGF‐A,VEGFR‐1,VEGFR‐2, Ang‐1, Ang‐2, Tie1, and Tie2, in 66 canine tumour tissues and in the normal tissues surrounding the tumours by quantitative real‐time PCR analysis. Our comparative analysis between canine tumour tissues and normal tissues revealed that several angiogenesis‐related genes, such as vascular endothelial growth factor (VEGF) and VEGF‐receptor genes, were significantly upregulated in canine tumour tissues when compared to the normal tissues. We also found that the angiopoietin (Ang)‐1/Ang‐2 gene expression ratio was lower in canine tumour tissues than in the normal tissues, suggesting less association between vascular endothelial cells and perivascular cells in the canine tumour tissues. Taken together, our results suggest that several angiogenesis‐related genes may contribute to the malignant progression of canine tumours via tumour angiogenesis. We investigated the expression of several angiogenesis‐related genes in 66 canine tumour tissues and in the normal tissues surrounding the tumours. We found that the angiopoietin (Ang)‐1/Ang‐2 gene expression ratio was lower in canine tumour tissues than in the normal tissues, suggesting less association between vascular endothelial cells and perivascular cells in the canine tumour tissues. [ABSTRACT FROM AUTHOR]

Carriers used to solubilize taxane chemotherapy drugs cause severe hypersensitivity. Nanoparticle formulations can provide improved dissolution and bioavailability of taxanes. Thus, a nanoparticulate, excipient‐free formulation of paclitaxel (CTI52010) was evaluated in tumour‐bearing dogs with intravenous and subcutaneous delivery. Tumour‐bearing dogs were treated with intravenous CTI52010 using a modified rapid dose escalation scheme. Subcutaneous administration was then planned for a small cohort of dogs for comparison. For both groups, serial blood samples were collected after first dosing for pharmacokinetic analysis by LCMSMS. Tumour response was measured using RECIST criteria. Toxicity was recorded using VCOG‐CTCAEv1.1. Fifteen dogs were treated with intravenous delivery at increasing dosages (80‐136 mg/m2), with one objective response in the urethral component of a prostatic carcinoma (probable transitional cell carcinoma) and four dogs with durable stable disease (two carcinomas, two sarcomas). Pharmacokinetic data indicate a rapid initial clearing of the drug from serum followed by an extended elimination half‐life, similar to normal dogs and suggesting reticuloendothelial clearance. Parameters and toxicity were highly variable and a maximally tolerated dosage could not be reliably confirmed. Three dogs were treated with subcutaneous delivery and no drug was detected in circulation, resulting in termination of the study. This novel formulation of paclitaxel is well tolerated in dogs and no unique toxicity or hypersensitivity was noted. The preliminary responses suggest biologic activity. The lack of systemic absorption after subcutaneous administration suggests a possible role for intratumoural anticancer therapy. [ABSTRACT FROM AUTHOR]

Primary pulmonary histiocytic sarcoma (PHS) has been reported, but is not well characterized. The aim of this retrospective study was to describe clinical characteristics, characterize prognostic factors and report the outcome of a larger group of dogs with primary PHS. Medical records of dogs diagnosed with primary PHS at 11 institutions were retrospectively reviewed. Thirty‐seven dogs were included; 13 received CCNU‐based chemotherapy alone, 18 received surgery and adjuvant CCNU‐based chemotherapy, 3 received medical management alone and 3 dogs received surgery alone. The overall median progression free survival (PFS) and the median survival (overall survival [OS]) were 197 and 237 days, respectively. Measurable responses were noted in dogs receiving only chemotherapy; however, responses were not durable with PFS (91 days) and OS times (131 days) shorter than overall medians. Dogs that received surgery and chemotherapy had significantly prolonged PFS (276 days, P = 0.001) and OS (374 days, P = 0.001), compared with dogs not receiving surgery. As only three dogs undergoing surgery did not receive chemotherapy, it is not possible to determine the contribution of chemotherapy as an adjuvant to surgery. Dogs without evidence of intra‐thoracic metastatic disease were much more likely to undergo surgery (odds ratio = 7.04; P = 0.018). While the presence of metastasis or clinical signs at diagnosis negatively impacted PFS, only the former negatively impacted OS. These data imply that dogs presenting with PHS amenable to surgery (ie, no clinical evidence of metastasis) benefit from surgical intervention; however, the lack of a comparable surgery alone group precludes assessment of the efficacy of post‐surgical adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

The use of the well‐known powerful antioxidant ascorbate has recently become more widespread in human medicine. Intravenous administration of high‐dose ascorbate has been demonstrated to exert anticancer effects. It has resulted in effective cell death in vitro and inhibition of tumour growth in vivo. The aim of the current study was to evaluate the effects of high‐dose ascorbate on canine melanoma in vitro. Four canine melanoma cell lines, UCDK9M1, UCDK9M3, UCDK9M4 and UCDK9M5 were treated with ascorbate for 2 hours at a range of millimolar concentrations (0‐20 mM) to investigate the resulting effects on cell viability. All four canine melanoma cell lines exhibited reduced viability in a dose‐dependent manner. Further investigation demonstrated that high‐dose ascorbate induced apoptosis via the activation of Bax. These findings suggest that high‐dose ascorbate has an anticancer effect on canine melanoma cell lines in vitro. With regard to clinical application, further in vivo investigation should be conducted. [ABSTRACT FROM AUTHOR]

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well‐known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow‐up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour‐related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment. [ABSTRACT FROM AUTHOR]

Transitional cell carcinoma (TCC) accounts for >90% of canine malignant tumours occurring in urinary bladder, and the prognosis is poor. Our previous study, using RNA sequencing, showed that human epidermal growth factor 2 (HER2) was the most activated upstream regulator related to carcinogenesis in canine TCC. The aim of this study was to examine the anti‐tumour effect of lapatinib, a tyrosine kinase inhibitor of HER2, on canine TCC cell lines in vitro and in vivo. Five canine TCC cell lines (TCCUB, Love, Sora, LCTCC, and MCTCC) were used. Western blotting showed that HER2 protein expression was observed in all of the canine TCC cell lines. Lapatinib inhibited phosphorylation of HER2 and cell growth in a dose‐dependent manner. Cell cycle analyses using flow cytometry showed that lapatinib significantly increased the sub‐G1 and G0/G1 phase fractions and significantly decreased the S and G2/M phase fractions in the cell lines (Sora and TCCUB). For the in vivo experiments, the canine TCC cells (Sora) were subcutaneously injected into nude mice. Six days after inoculation, lapatinib (100 mg/kg) or vehicle was administered daily via intraperitoneal administration for 14 days. Tumour volume was significantly smaller in the lapatinib group compared with the vehicle control group. Histologically, lapatinib significantly increased necrotic areas in the tumour tissues. These findings suggest that lapatinib exerts anti‐tumour effects on canine TCC cells by inhibiting HER2 signalling and inducing cell cycle arrest. [ABSTRACT FROM AUTHOR]

Canine mammary tumours (CMTs) are common neoplasms in dogs that feature many of the clinical, genetic and molecular characteristics of human breast cancer. Despite their high metastatic potential, few adjuvant chemotherapeutic treatment options exist for malignant CMTs, and the development of novel, targeted pharmacological approaches will require a better understanding of their pathogenesis. As recent evidence suggests that dysregulated Hippo signalling is involved in the development and progression of breast cancer, we sought to determine if this pathway could also play a role in CMT. The expression of the Hippo signalling effectors YAP and TAZ was analysed by immunoblotting and immunohistochemistry in samples including normal mammary gland, lobular hyperplasia, benign tumours and malignant tumours of all grades. We found a significant increase in TAZ (but not YAP) expression occurred in lobular hyperplasia relative to normal mammary gland, suggesting a role for TAZ in non‐neoplastic epithelial proliferation. Nuclear expression of both TAZ and YAP were significantly higher in malignant tumours than in benign ones, suggesting that Hippo dysregulation could play a role in CMT malignant transformation. No differences in YAP or TAZ expression were detected between grades of malignant tumours. Together, our results indicate that alterations in Hippo signalling may play a role in the pathogenesis of CMT, in a manner similar to breast cancer. Hippo pathway components may therefore represent targets for the development of novel chemotherapeutic agents that could be useful for the treatment of both the human and canine diseases. [ABSTRACT FROM AUTHOR]

Canine T cell lymphoma has previously been found to be a poor prognostic indicator compared with its B cell counterpart. The cyclophosphamide, doxorubicin, vincristine, and prednisolone protocol is widely accepted as a first line treatment for canine lymphoma. There have been several studies investigating alternative protocols for T cell lymphoma. This study investigated the use of a modified lomustine, vincristine, procarbazine and prednisolone protocol as a first line treatment in 35 dogs with T Cell lymphoma. Median progression free survival (PFS) time for all 35 dogs was 431 days with a 6‐month, 1‐year, 2‐year, and 3‐year PFS of 69%, 54%, 29%, and 12%. Median survival time (MST) was 507 days. Twenty‐nine dogs attained a complete response and had a median PFS time of 509 days. Thirty dogs experienced adverse events during the protocol, with 73% of these being grade 1 or 2. This protocol has shown increased median PFS time and MST compared with previous studies and suggests its use as a first line chemotherapy protocol against canine T cell lymphoma. [ABSTRACT FROM AUTHOR]

Canine diffuse large B‐cell lymphoma (DLBCL), the most common hematologic malignancy of dogs, is associated with poor overall survival. The lack of conventional chemotherapies with sustainable efficacy warrants investigation of novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule NEDD8‐activating enzyme inhibitor. In human activated B‐cell‐like (ABC) diffuse large B‐cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage and G1 cell cycle arrest by inhibiting the nuclear factor‐κB (NF‐κB) pathway. Genomic and transcriptomic studies showed that the NF‐κB pathway is deregulated in canine DLBCL. Our results showed that pevonedistat treatment significantly reduces the viability of canine DLBCL cells by inducing G1 cell cycle arrest and apoptosis. Pevonedistat treatment inhibits NF‐κB pathway activation and downregulates NF‐κB target genes in canine DLBCL. Moreover, administration of pevonedistat to mice bearing canine DLBCL xenograft tumours resulted in tumour regression. Our in vivo and in vitro studies provide justification for future clinical application of pevonedistat as a potential new anti‐cancer therapy that may benefit both canine and human species. [ABSTRACT FROM AUTHOR]

Mammary tumours are the most frequent in female dogs as in women and half are malignant. Tumorigenicity and invasiveness are important acquired characteristics for the development and progression of cancers and could be regulated by transcription factors associated with epithelial‐mesenchymal transition (EMT) as ZEB1, ZEB2, SNAI1, SLUG and STAT3. Thus, here, we evaluate the expression of EMT‐associated transcription factors in canine mammary cancer (CMC) cell lines characterized for invasiveness and tumorigenicity to determine if these could be considered good targets for future development of therapies. Five CMC cell lines were characterized regarding their morphology, doubling time and expression of intermediate and actin filaments. In addition, gene expression of SLUG, STAT3, ZEB1, ZEB2 and CDH1, tumorigenicity and invasiveness were assessed. Two of these cells presented an epithelial‐like morphology (E20 and E37) and three a mesenchymal‐like morphology (M5, M25 and CF41.Mg). M25 and CF41.Mg presented higher invasiveness. Furthermore, only mesenchymal‐like cells formed tumorspheres and CF41.Mg made more and larger tumorspheres. The mesenchymal‐like cells are more malignant than the epithelial‐like cells being the CF41.Mg the most malignant. This cell presented higher ZEB1 and ZEB2 and lower CDH1 gene expression. Finally, our results revealed that there is a positive correlation between ZEBs and the tumorsphere number and size. In conclusion, these findings support ZEB1 and ZEB2 as potential therapeutic targets for CMC cells, demonstrating a great potential of canine models for comparative and translational studies. [ABSTRACT FROM AUTHOR]

Curcumin has well‐established anti‐cancer properties in vitro, however, its therapeutic potential has been hindered by its poor bioavailability. Lipocurc is a proprietary liposome‐encapsulated curcumin formulation that enables intravenous delivery and has been shown to reach its highest concentration within lung tissue. The goal of this study was to characterize the anti‐cancer and anti‐angiogenic activity of Lipocurc in vitro, in addition to evaluating Lipocurc infusions in dogs with naturally occurring cancer. We therefore evaluated the effect of Lipocurc, relative to free curcumin, on the viability of canine osteosarcoma, melanoma and mammary carcinoma cell lines, as well as the ability of Lipocurc to inhibit endothelial cell viability, migration and tube formation. We also undertook a pilot clinical trial consisting of four weekly 8‐hour Lipocurc infusions in 10 cancer‐bearing dogs. Tumour cell proliferation was inhibited by curcumin at concentrations exceeding those achievable in the lung tissue of dogs. Similarly, equivalent high concentrations of Lipocurc and curcumin also inhibited endothelial cell viability, migration and tube formation. Four out of six dogs completing planned infusions of Lipocurc experienced stable disease; however, no radiographic responses were detected. [ABSTRACT FROM AUTHOR]

Osteosarcoma, a common malignancy in large dog breeds, typically metastasises from long bones to lungs and is usually fatal within 1 to 2 years of diagnosis. Better therapies are needed for canine patients and their human counterparts, a third of whom die within 5 years of diagnosis. We compared the in vitro sensitivity of canine osteosarcoma cells derived from 4 tumours to the currently used chemotherapy drugs doxorubicin and carboplatin, and 4 new anti‐cancer drugs. Agents targeting histone deacetylases or PARP were ineffective. Two of the 4 cell lines were somewhat sensitive to the BH3‐mimetic navitoclax. The proteasome inhibitor bortezomib potently induced caspase‐dependent apoptosis, at concentrations substantially lower than levels detected in the bones and lungs of treated rodents. Co‐treatment with bortezomib and either doxorubicin or carboplatin was more toxic to canine osteosarcoma cells than each agent alone. Newer proteasome inhibitors carfilzomib, ixazomib, oprozomib and delanzomib manifested similar activities to bortezomib. Human osteosarcoma cells were as sensitive to bortezomib as the canine cells, but slightly less sensitive to the newer drugs. Human osteoblasts were less sensitive to proteasome inhibition than osteosarcoma cells, but physiologically relevant concentrations were toxic. Such toxicity, if replicated in vivo, may impair bone growth and strength in adolescent human osteosarcoma patients, but may be tolerated by canine patients, which are usually diagnosed later in life. Proteasome inhibitors such as bortezomib may be useful for treating canine osteosarcoma, and ultimately may improve outcomes for human patients if their osteoblasts survive exposure in vivo, or if osteoblast toxicity can be managed. [ABSTRACT FROM AUTHOR]

Metastatic rates and survival times of canine anal sac gland adenocarcinomas (ASGACs) vary among studies, making prognostication difficult. Little is known about the prognostic significance of histopathology of ASGACs. This retrospective study investigated associations between histological features, clinical presentation and outcome for 39 ASGACs. Most tumours were incompletely excised (62%) and had moderate to marked peripheral infiltration (74%). The predominant growth pattern was solid, tubules/rosettes/pseudorosettes and papillary in 49%, 46% and 5% of the cases, respectively. Nuclear pleomorphism was either moderate (77%) or mild (23%). Necrosis and lymphovascular invasion were present in 54% and 10% of the cases, respectively. All histological features except mitotic count and necrosis were associated with nodal metastasis at presentation. A statistically significant poorer outcome was identified for tumours with a solid growth pattern, moderate or marked peripheral infiltration, necrosis and lymphovascular invasion. These results need further validation in a larger cohort of dogs. [ABSTRACT FROM AUTHOR]

A previous study found that minichromosome maintenance protein 7 (MCM7) score was associated with prognosis in dogs with cutaneous mast cell tumours (MCTs) independent of histological grade. The primary aim of this study was to validate this score in a different cohort of dogs focusing exclusively on patients with Patnaik intermediate grade MCTs treated with surgery alone and followed for a minimum of 1 year. A secondary aim was to evaluate the prognostic performance of MCM7 in relation to Kiupel histological grade, mitotic index (MI) and Ki67 index in the same cohort of dogs. Ninety dogs were identified, 82 were low Kiupel grade and 8 were high Kiupel grade. Seventy‐two dogs were alive after a median follow‐up of 1136 days and 18 dogs died of MCT‐related causes after a median of 116 days. A MI threshold of 5 was associated with a sensitivity of 0.39 and a specificity of 0.99 in predicting MCT‐related death; for Ki67 a threshold of 0.018 was associated with a sensitivity of 0.78 and a specificity of 0.83; and for MCM7 a threshold of 0.18 gave a sensitivity of 0.83 and a specificity of 0.86. Combining MI, Ki67 and MCM7 showed an improved accuracy of predicting death compared with each individual variable. Therefore, performing Ki67 and MCM7 in dogs with GII MCT, low Kiupel grade and low MI might be a consideration. [ABSTRACT FROM AUTHOR]

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May‐Grünwald‐Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good‐quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high‐grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS‐stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high‐grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membrane‐bound vesicles produced by cells, known to play a key role in cell‐to‐cell communication. They exert pleiotropic biological functions via the horizontal transfer of bioactive molecules (DNA, RNAs, proteins, and lipids) within the tumour microenvironment and throughout the body. In human cancer, EVs are known to interfere with pathways that lead to tumour progression and are used as novel cancer biomarkers. In veterinary medicine, very little is known on cancer‐derived EVs. In this study, we preliminarily characterized EVs in mammary gland cancer of dogs and cats. EVs were isolated by ultracentrifugation from canine (CYPp), feline (FMCp) and human (MCF7) mammary tumour cell lines. EVs were visualized by transmission electron microscopy (TEM), counted using nanoparticle tracking analysis (NTA) and characterized by immunogold (CD63 and Alix) and western blot (Alix and TSG101). Additionally, EV production by "donor" cells (palmtdTomato+) and uptake by "recipient" cells (GFP+) were assessed. EVs were successfully isolated from all 3 cell lines by ultracentrifugation. Membrane‐bound structures (50‐400 nm) were identified by TEM and were positive for both CD63 and Alix at immunogold. Western blot showed positivity of EVs to Alix and TSG101. NTA analysis detected EVs from cell culture media ranging from 1.67 to 2.56 × 102 as number of EVs/cell and from 80 to 600 nm in size. Confocal microscopy identified the presence of palmtdTomato+ EVs into the cytoplasm of GFP+ cells. This preliminary study identified and characterized canine and feline mammary tumour cell‐derived EVs, opening in veterinary medicine a new interesting unexplored field with several applications and limitless potential. [ABSTRACT FROM AUTHOR]

Metastasis to regional lymph nodes (RLNs) in dogs with cutaneous mast cell tumour (cMCT) has been correlated with shortened survival time and higher risk of spread to distant sites. In the present study, extirpation of non‐palpable or normal‐sized RLNs was included in the surgical management of cMCT in dogs. Correlations between histological nodal status (HN0‐3) and tumour variables were analysed. Ninety‐three dogs with single cMCT without distant metastasis that underwent wide surgical excision of the primary tumour and extirpation of non‐palpable or normal‐sized RLN were included. The association between HN (HN0 vs HN > 0; HN0‐1 vs HN2‐3) and tumour variables (site, longest diameter, ulceration, 3‐tier and 2‐tier histological grades) was analysed by a generalized linear model with multinomial error. Then, 33 (35.5%) RLNs were HN0, 14 (15%) were HN1, 26 (28%) were HN2 and 20 (21.5%) were HN3. The presence of positive (HN > 0) RLN was significantly associated with cMCT larger than 3 cm. No other association was statistically significant. Non‐palpable/normal‐sized RLN in dogs with cMCT can harbour histologically detectable metastatic disease in nearly half of the cases. Extirpation of the RLN should always perfomed to obtain a correct staging of the disease, even in the absence of clinical suspicion of metastasis. Further studies should evaluate the possible therapeutical effect of the tumour burden reduction obtained by exrtipartion of a positive RLN. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OSA) is the most common malignant bone cancer in children and dogs. The therapeutic protocols adopted for dogs and humans are very similar, involving surgical options such as amputation. Besides surgical options, radiotherapy and chemotherapy also are adopted. However, hematologic, gastrointestinal and renal toxicity may occur because of chemotherapy treatments. Recent study clearly showed that mesenchymal stem cells (MSCs) combined with recombinant human bone morphogenetic protein (rhBMP‐2) may be associated with decreases of the tumorigenic potential of canine OSA. The aim of this study was to analyse the efficacy of chemotherapy with carboplatin and rhBMP‐2 with MSCs in a canine OSA in vivo model. Canine OSA cells were implanted in mice Balb‐c/nude with MSCs, rhBMP‐2 and carboplatin. Flow cytometry and PCR for markers involved in tumour suppression pathways were analysed. Results showed that the combination of MSCs and rhBMP‐2 reduced tumour mass and infiltration of neoplastic cells in tissues more efficiently than carboplatin alone. Thus it was demonstrated that the use of rhBMP‐2 and MSCs, in combination with conventional antineoplastic, may be an efficient treatment strategy. [ABSTRACT FROM AUTHOR]

Intracranial gliomas are a common malignancy in dogs, and are associated with a poor prognosis due to their aggressive nature and a lack of clinically effective treatments. The efficacies of various treatment modalities for canine brain tumours have been previously described, though little data exist on the use of cytotoxic chemotherapy. A comparative retrospective study, including 40 cases from 5 northeastern US veterinary hospitals, from 2008 to 2017, was conducted. Variables analysed in this study with relation to overall survival and prognostic significance included: age, sex, clinical signs, clinical sign duration, tumour location and treatment protocol used. Dogs with presumptive intracranial gliomas treated with lomustine chemotherapy lived longer (median, 138 days) than those treated exclusively with symptomatic care (median, 35 days; P = .0026 log‐rank, 0.0138 Wilcoxon). Additionally, a duration of clinical signs ≥16 days prior to diagnosis (median, 109 days) was associated with a longer survival than a duration <16 days prior (median, 25 days; P = .0100 log‐rank, 0.0322 Wilcoxon). Lomustine‐associated side effects included neutropenia in 46% of dogs, anaemia in 15% and thrombocytopenia in 15%. Potential renal and hepatotoxicity based on increased BUN and/or creatinine and ALT values were reported in 15% and 50% of dogs, respectively. This study provides evidence that lomustine therapy may be effective in prolonging survival in dogs with intracranial gliomas and should be considered as a potential treatment option. Although lomustine‐related toxicities are fairly common, they are rarely life threatening and often do not result in discontinuation of therapy. [ABSTRACT FROM AUTHOR]

Literature describing medical treatment of canine prostatic carcinoma (PC) is sparse. The aims of this study were to assess outcomes, including time to progression (TTP) and median survival time (MST), of canine PC treated with non‐steroidal anti‐inflammatory drugs (NSAIDs) and/or chemotherapy, and to identify prognostic factors. Records from 8 institutions were searched for dogs with cytologically or histologically confirmed PC without bladder involvement: 67 dogs were included. Presenting signs were urinary (25), gastrointestinal ([GI], 11) and systemic (3); 16 dogs had GI and urinary signs, 7 dogs had systemic signs with concurrent GI or urinary signs and in 5 dogs the tumour was an incidental finding. Out of 27 dogs, 9 (33%) had positive urine culture. Metastases were identified in 26 dogs to lymph nodes (19), lungs (10), bone (2) and liver (1). Treatment included NSAIDs and chemotherapy (32), NSAIDs alone (31) and chemotherapy alone (4). The overall MST was 82 days (range 9‐752) and median TTP was 63 days (range 9‐752). Dogs receiving NSAIDs combined with chemotherapy experienced a significantly longer MST (106 vs 51 days; P = .035) and TTP (76 vs 44 days; P = .02) compared to dogs receiving NSAIDs alone. Intact dogs and those with metastatic disease had significantly shorter MST (31 vs 90 days, P = .018 and 49 vs 109 days, P = .037, respectively); intact dogs also had significantly shorter TTP (25 vs 63 days, P = .0003). This study suggests that a combination of NSAIDs and chemotherapy may improve outcomes in canine PC. Metastatic disease and being entire negatively influenced prognosis. [ABSTRACT FROM AUTHOR]

Combretastatin A4‐phosphate (CA4P) is an anti‐tumour vascular targeting agent which selectively blocks tumour blood flow. Research on CA4P in rodent tumour models is extensive; however, knowledge of its effect on spontaneous cancer is scarce. This study was conducted in canine patients with spontaneous solid tumours. The goal was to assess the toxicity and efficacy of CA4P in various spontaneous tumour types. Eight dogs with spontaneous tumours were enrolled and treated with a single dose of 75 mg m−2 intravenous CA4P. The dogs were screened and monitored before and after injection. Pre‐ and post‐treatment tumour blood flow was analysed in vivo by power Doppler ultrasound (PDUS) and contrast‐enhanced ultrasound (CEUS). Vessel destruction and tumour necrosis were evaluated by histopathology. Clinically relevant toxicity was limited to one case of temporary tetraparesis; other adverse events were mild. Significant cardiovascular changes were mostly confined to changes in heart rate and cTnI levels. Macroscopic tumour size reduction was evident in 2 dogs. Based on PDUS and CEUS, CA4P induced a significant decrease in vascular index and tumour blood flow. Post‐treatment, histopathology revealed a significant increase of necrotic tumoural tissue and a significant reduction in microvessel density in tumoural tissue. Anti‐vascular and necrotizing effects of CA4P were documented in a variety of canine spontaneous cancers with only minimal side effects. This is the first study reporting the administration of CA4P to canine cancer patients with in vivo and ex vivo assessment, and a first step toward implementing CA4P in combination therapies in veterinary oncology patients. The use of CA4P in canine patients was approved and registered by the Belgian Federal Agency for Medicines and Health Products (FAMHP) (approval number 0002588, registration number 6518 ID 2F12). [ABSTRACT FROM AUTHOR]

Intestinal T‐cell lymphoma is being more frequently diagnosed in dogs owing to the wide availability of endoscopy and clonality analysis in veterinary medicine. However, no epidemiological study on intestinal T‐cell lymphoma has been previously performed, and hence, information about dog breed, age and sex distributions of intestinal T‐cell lymphoma has largely remained unclear. In this study, breed predisposition to canine intestinal T‐cell lymphoma was determined by calculating odds ratios and 95% confidential intervals. Of the 43 breeds identified, 7 appeared to have an increased risk of developing intestinal T‐cell lymphoma, including Shiba dogs, German shepherds, Cairn terriers, Boston terriers, Papillons, Pugs and Maltese. Immunohistochemistry of representative Shiba cases revealed ubiquitous cytotoxic immunophenotype in both large and small cell lymphomas. Interestingly, CD20 co‐expression was observed in 11% of cases. It could potentially be aberrant expression of CD20 or neoplastic transformation of a normal subset of CD20‐positive T‐cells. A comparison of mean age between representative breeds revealed that Shiba dogs were slightly younger than Miniature Dachshunds (P <.05). However, there was no difference in survival between the 2 breeds. As Shiba dogs are predisposed to chronic enteropathy, there may be underlying inflammatory process contributing to lymphomagenesis of intestinal T‐cell lymphoma in this breed. Our findings provide insights into the underlying pathogenesis of breed‐specific canine intestinal T‐cell lymphoma. [ABSTRACT FROM AUTHOR]

A 7-year-old male intact border terrier (8.5 kg) was presented with a large, painless mass apical to the right maxillary incisors. Diagnostic imaging and histopathology confirmed the diagnosis of periapical cyst due to a nonvital maxillary incisor. Extensive cysts are often multilocular and therefore difficult to debride without risk of iatrogenic damage. Complete resection can cause damage to adjacent structures and may compromise function. Due to the large size of the cyst, it was decided to perform staged treatment with extraction of the nonvital tooth and marsupialization. Following marsupialization, gradual bone regrowth caused size reduction. The stoma from the marsupialization was kept open for 8.5 months before the cyst was curetted and the wound closed. Complete obliteration of the cyst cavity was seen at short- and long-term follow-up examinations (7 and 24 months after curettage, respectively). [ABSTRACT FROM AUTHOR]