Treatment of mammary gland tumors in bitches: effects of sodium dichloroacetate as neoadjuvant therapy.

Mastectomy is the standard treatment for mammary gland tumors in dogs. In addition to traditional therapy, sodium dichloroacetate (DCA) can act as target therapy, as it may promote autophagy, reduce metastatic potential, and tumor proliferation in mammary tumor cell lines. This study aimed to analyze the effects of DCA as preoperative therapy for mammary tumors in bitches. Nineteen animals were selected, and they received DCA at a dose of 10 mg/kg orally every 12 hr, for 15 days. The periodic evaluation included hematological analysis (complete blood count and biochemical markers), evaluation of gastrointestinal adverse effects, evaluation of tumor volume, histopathological analysis, and immunohistochemical evaluation (Ki67 and cyclooxygenase-2/COX-2 markers). After treatment, there was a significant reduction in hematocrit (P=0.02) and leukocyte (P=0.04) means. Despite the variations for these two hematological parameters, the means remained within the reference range for the species. There were two cases of vomiting and one case of diarrhea. Most cases were classified as carcinoma in mixed tumor (n=7, 36.8%), followed by solid carcinoma (n=6, 31.6%). Nine cases (47.4%) showed reduced tumor volume, nine (47.4%) had stable disease, and one showed progressive disease. While there was no sample with a COX-2 score higher than 6, tumor samples with COX-2 scores 3 and 4 were significantly associated with stable disease or progression. DCA preoperative treatment for bitches with mammary gland tumors showed safety and potential cytoreduction in some cases.

Comparative characterization of two monoclonal antibodies targeting canine PD-1.

Monoclonal antibodies targeting immune checkpoints have revolutionized oncology. Yet, the effectiveness of these treatments varies significantly among patients, and they are associated with unexpected adverse events, including hyperprogression. The murine research model used in drug development fails to recapitulate both the functional human immune system and the population heterogeneity. Hence, a novel model is urgently needed to study the consequences of immune checkpoint blockade. Dogs appear to be uniquely suited for this role. Approximately 1 in 4 companion dogs dies from cancer, yet no antibodies are commercially available for use in veterinary oncology. Here we characterize two novel antibodies that bind canine PD-1 with sub-nanomolar affinity as measured by SPR. Both antibodies block the clinically crucial PD-1/PD-L1 interaction in a competitive ELISA assay. Additionally, the antibodies were tested with a broad range of assays including Western Blot, ELISA, flow cytometry, immunofluorescence and immunohistochemistry. The antibodies appear to bind two distinct epitopes as predicted by molecular modeling and peptide phage display. Our study provides new tools for canine oncology research and a potential veterinary therapeutic.

Treatment of feline intermediate to high-grade alimentary lymphoma: A retrospective evaluation of 55 cats treated with the VAPC combination chemotherapy protocol (2017-2021).

The most commonly utilized protocols to treat lymphoma in cats employ vincristine, cyclophosphamide and prednisone; with additional drugs sometimes used including L-asparaginase and doxorubicin. Medical records were reviewed for 55 cats with alimentary lymphoma treated with a novel multiagent protocol using prednisolone, L-asparaginase, doxorubicin, vinblastine instead of vincristine, a higher dosage of cyclophosphamide and oral procarbazine (VAPC protocol). Outcomes evaluated were response to therapy, toxicity and progression-free survival (PFS). Grade 3 or 4 neutropenia was the most common treatment-related reason for chemotherapy dosage adjustment, occurring in 8 of 52 cats receiving vinblastine, 7 of 55 cats receiving cyclophosphamide and 1 of 40 cats receiving doxorubicin, but febrile neutropenia was identified in only two cats. Of 38 cats receiving chemotherapy for measurable disease, 26 (68.4%) achieved complete response (CR). Three cats achieved a partial response and 9 cats failed to achieve a remission. There were no identified factors influencing whether a cat was likely to achieve CR. For all 55 cats (including those receiving chemotherapy and surgery), median PFS was 184 days with 1, 2 and 3-year survival rates of 35.4%, 26.5% and 26.5%, respectively. On multivariate analysis, 40 cats that achieved CR had a median survival time of 341 days (78 days for PR, 45 days for NR); PFS times were also significantly affected by lymphocyte:monocyte L:M ratio (>3.4 = 700 days vs. ≤3.4 = 126 days) and B-cell versus T-cell phenotype (220 days vs. 42 days, respectively).

Anaesthesia in Veterinary Oncology: The Effects of Surgery, Volatile and Intravenous Anaesthetics on the Immune System and Tumour Spread.

Throughout the course of oncological disease, the majority of patients require surgical, anaesthetic and analgesic intervention. However, during the perioperative period, anaesthetic agents and techniques, surgical tissue trauma, adjuvant drugs for local pain and inflammation and other non-pharmacological factors, such as blood transfusions, hydration, temperature and nutrition, may influence the prognosis of the disease. These factors significantly impact the oncologic patient's immune response, which is the primary barrier to tumour progress, promoting a window of vulnerability for its dissemination and recurrence. More research is required to ascertain which anaesthetics and techniques have immunoprotective and anti-tumour effects, which will contribute to developing novel anaesthetic strategies in veterinary medicine.

Identifying the Risk Factors for Malignant Mammary Tumors in Dogs: A Retrospective Study.

Mammary cancer is one of the main causes of death in female dogs worldwide, considering that many risk factors are involved in its development. This study aimed to elucidate the relationship between epidemiological and clinical risk factors with the histopathological diagnosis of malignant mammary tumors in dogs treated at the Veterinary Hospital of the Federal University of Uberlândia, which has one of the first veterinary oncology services in Brazil. A retrospective matched case-control study was conducted to identify risk factors for the development of malignant mammary tumors in dogs. The variables analyzed were size dog, breed, housing, type of diet, and body score. Potential risk factors were selected by univariate analysis (p < 0.25) before multivariate forward binary logistic regression. The most frequent benign tumor was the benign mixed tumor (35.2%), and the most frequent malignant tumor was the mixed carcinoma (27.4%). Size dog, breed, housing, and overweight are predictors of malignant mammary tumors in dogs. The highest risk of developing malignant mammary tumors is associated with large female dogs, Yorkshire or Poodle breeds, living outside the home, or being overweight.

Evaluation of Surgical Aid of Methylene Blue in Addition to Intraoperative Gamma Probe for Sentinel Lymph Node Extirpation in 116 Canine Mast Cell Tumors (2017-2022).

Methylene Blue (MB) is combined with radiopharmaceutical for intraoperative sentinel lymph node (SLN) mapping, but its role during SLN extirpation has not been investigated yet in veterinary medicine. The aim of this study was to assess whether MB increased surgical detection of SLN beyond the use of intraoperative gamma-probe (IGP) alone in clinically node-negative dogs with mast cell tumors (MCTs) following the detection of sentinel lymphocentrums (SLCs) via preoperative planar lymphoscintigraphy. Dogs enrolled underwent MCT excision and SLC exploration guided by both MB and IGP. Data recorded for each SLN were staining (blue/non-blue), radioactivity (hot/non-hot), and histopathological status (HN0-1 vs. HN2-3). A total of 103 dogs bearing 80 cutaneous, 35 subcutaneous, and 1 mucocutaneous MCTs were included; 140 SLCs were explored, for a total of 196 SLNs removed. Associating MB with IGP raised the SLNs detection rate from 90% to 95%. A total of 44% of SLNs were metastatic: 86% were blue/hot, 7% were only blue, 5% were only hot, and 2% were non-blue/non-hot. All HN3 SLNs were hot. Combining MB with IGP can increase the rate of SLN detection in dogs with MCTs; nonetheless, all lymph nodes identified during dissection should be removed, as they might be unstained but metastatic.

Sirtuin 1 Expression in Canine Mammary Tumors: A Pilot Study.

Sirtuin 1 (SIRT1) is a protein involved in aging, cell protection, and energy metabolism in mammals. Recently, SIRT1 has been intensively studied in medical oncology, but the role of SIRT1 is still controversial, as it has been proposed as both an oncogene and a tumor suppressor. The aim of this study is to investigate the expression of SIRT1 by immunohistochemistry in canine mammary tissues, and by Western blot and immunofluorescence analysis in different canine mammary cell lines. Our results showed a decrease in SIRT1 expression from normal mammary gland tissue, and from benign and well-differentiated malignant tumors (G1) to less differentiated ones (G2-G3). Furthermore, a shift in the subcellular localization of SIRT1 from the nucleus to the cytoplasm was observed in less differentiated malignant tumors. However, further studies are needed to investigate the subcellular localization of SIRT1 in canine cancer cells and the role it may play in oncogenesis in animals.

Automated diagnosis of 7 canine skin tumors using machine learning on H&E-stained whole slide images.

Microscopic evaluation of hematoxylin and eosin-stained slides is still the diagnostic gold standard for a variety of diseases, including neoplasms. Nevertheless, intra- and interrater variability are well documented among pathologists. So far, computer assistance via automated image analysis has shown potential to support pathologists in improving accuracy and reproducibility of quantitative tasks. In this proof of principle study, we describe a machine-learning-based algorithm for the automated diagnosis of 7 of the most common canine skin tumors: trichoblastoma, squamous cell carcinoma, peripheral nerve sheath tumor, melanoma, histiocytoma, mast cell tumor, and plasmacytoma. We selected, digitized, and annotated 350 hematoxylin and eosin-stained slides (50 per tumor type) to create a database divided into training, n = 245 whole-slide images (WSIs), validation (n = 35 WSIs), and test sets (n = 70 WSIs). Full annotations included the 7 tumor classes and 6 normal skin structures. The data set was used to train a convolutional neural network (CNN) for the automatic segmentation of tumor and nontumor classes. Subsequently, the detected tumor regions were classified patch-wise into 1 of the 7 tumor classes. A majority of patches-approach led to a tumor classification accuracy of the network on the slide-level of 95% (133/140 WSIs), with a patch-level precision of 85%. The same 140 WSIs were provided to 6 experienced pathologists for diagnosis, who achieved a similar slide-level accuracy of 98% (137/140 correct majority votes). Our results highlight the feasibility of artificial intelligence-based methods as a support tool in diagnostic oncologic pathology with future applications in other species and tumor types.

Cancerogenic parasites in veterinary medicine: a narrative literature review.

Parasite infection is one of the many environmental factors that can significantly contribute to carcinogenesis and is already known to be associated with a variety of malignancies in both human and veterinary medicine. However, the actual number of cancerogenic parasites and their relationship to tumor development is far from being fully understood, especially in veterinary medicine. Thus, the aim of this review is to investigate parasite-related cancers in domestic and wild animals and their burden in veterinary oncology. Spontaneous neoplasia with ascertained or putative parasite etiology in domestic and wild animals will be reviewed, and the multifarious mechanisms of protozoan and metazoan cancer induction will be discussed.

Exploring the link between viruses and cancer in companion animals: a comprehensive and comparative analysis.

Currently, it is estimated that 15% of human neoplasms globally are caused by infectious agents, with new evidence emerging continuously. Multiple agents have been implicated in various forms of neoplasia, with viruses as the most frequent. In recent years, investigation on viral mechanisms underlying tumoral transformation in cancer development and progression are in the spotlight, both in human and veterinary oncology. Oncogenic viruses in veterinary medicine are of primary importance not only as original pathogens of pets, but also in the view of pets as models of human malignancies. Hence, this work will provide an overview of the main oncogenic viruses of companion animals, with brief notes of comparative medicine.

A pilot study of chemotherapy combinations in rats: Focus on mammary cancer treatment in female dogs.

The use of combined chemotherapy is an essential alternative in treating breast cancer. However, knowledge of the pharmacokinetics of drugs is necessary to obtain maximum efficiency of the protocol and reduce adverse reactions. This study suggests for the first time the effect of the association of carboplatin with ivermectin and carboplatin with cyclophosphamide. This investigation was performed with 36 healthy Wistar rats, divided into four groups: group control, carboplatin (C), carboplatin preceded by ivermectin (C + IV), and carboplatin associated with cyclophosphamide (C + CI). Plasma concentrations quantification was performed using the High-Performance Liquid Chromatographic (HPLC) equipment with an Ultraviolet (UV) detector at eight different time points. Then, the animal was euthanized and necropsied. The bioanalytical method was validated for the two matrices (dogs and rats' plasma), with full validation in female dogs and partial validation in rats, as recommended by the EMA. In both matrices, the method was linear and reproducible. Here, we show the results in female rats' plasma. When comparing the experimental rats' groups (C; C + IV, and C + CI), there is a tendency to increase the bioavailability of carboplatin when used in association, a slight increase for C + IV and more evident to the C + CI group with an AUC rise higher than 2-fold (AUC0-∞ = 2983.61 for C; 4459.06 for C + CI; 7064.68 for C + CI min·mg·mL-1). The blood count, biochemistry profile, and histopathology of the organs revealed only alterations inherent to the metabolic effects of the drugs used. The carboplatin association with ivermectin appeared safe for this pilot group. We believe the carboplatin dose can be maintained without risk to the patient. However, in the carboplatin association with cyclophosphamide, a slight reduction in carboplatin's amount is suggested, seeking to avoid increased effects due to cyclophosphamide. Thus, studies with a more significant number per group must confirm the relevance of this pilot study.

The Use of Oncept Melanoma Vaccine in Veterinary Patients: A Review of the Literature.

The Oncept melanoma vaccine is xenogeneic DNA vaccine targeting tyrosinase. It is USDA approved for treatment of stage II to III canine oral melanoma and is also used off-label for melanomas arising in other locations and in other species. While the vaccine appears safe, the published data is mixed as to whether it provides a survival benefit, and the use of the vaccine is somewhat controversial in the veterinary oncology community. In this paper, the published literature describing the use of Oncept is reviewed and evaluated.

Vet-OncoNet: Malignancy Analysis of Neoplasms in Dogs and Cats.

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors' topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.

Pathological aspects of cutaneous mast cell tumors with metastases in 49 dogs.

Cutaneous mast cell tumor (MCT) is one of the most frequent cutaneous neoplasms of dogs and may vary from well-differentiated to aggressive tumors with metastasis. The authors retrospectively described the gross and histologic aspects of metastatic MCT in 49 dogs. Primary MCT was most commonly identified in the inguinal region (14/35; 40%), and at necropsy multiple, cutaneous nodules were frequently reported (23/49; 47%). All primary MCT were classified as high-grade neoplasms, and metastases involved the lymph nodes (47/49; 96%), spleen (33/49; 67%), liver (29/49; 59%), bone marrow (20/49; 41%), kidneys (16/49; 33%), and heart (14/49; 29%), while the lungs were less commonly affected (9/49; 18%). The main gross findings included lymphadenomegaly in 47 cases; splenomegaly in 28 cases, with splenic nodules in 13 dogs; hepatomegaly in 28 cases, with white pinpoint foci in 9 cases; nodules on the capsular surface of the kidneys in 9 dogs; and epicardial nodules in 6 cases. Histologically, the lymph nodes were largely obliterated by neoplastic mast cells, while in the spleen, neoplastic cells were multifocally scattered (16/33; 48%), arranged in nodules (10/33; 30%), or obliterated the parenchyma (9/33; 27%). In the liver, the neoplastic cells mainly infiltrated the sinusoids (24/29; 83%), but were also arranged in random nodules (10/29; 34%). Interstitial and nodular metastases were observed in the kidneys and the heart. Grossly unapparent metastases were common in the heart (6/14; 43%), kidneys (4/16; 25%), and lungs (6/9). KIT III and KIT II staining patterns were observed in 29 and 20 cases, respectively.

Multimodal Approach of Optical Coherence Tomography and Raman Spectroscopy Can Improve Differentiating Benign and Malignant Skin Tumors in Animal Patients.

As in humans, cancer is one of the leading causes of companion animal mortality. Up to 30% of all canine and feline neoplasms appear on the skin or directly under it. There are only a few available studies that have investigated pet tumors by biophotonics techniques. In this study, we acquired 1115 optical coherence tomography (OCT) images of canine and feline skin, lipomas, soft tissue sarcomas, and mast cell tumors ex vivo, which were subsequently used for automated machine vision analysis. The OCT images were analyzed using a scanning window with a size of 53 × 53 µm. The distributions of the standard deviation, mean, range, and coefficient of variation values were acquired for each image. These distributions were characterized by their mean, standard deviation, and median values, resulting in 12 parameters in total. Additionally, 1002 Raman spectral measurements were made on the same samples, and features were generated by integrating the intensity of the most prominent peaks. Linear discriminant analysis (LDA) was used for sample classification, and sensitivities/specificities were acquired by leave-one-out cross-validation. Three datasets were analyzed-OCT, Raman, and combined. The combined OCT and Raman data enabled the best sample differentiation with the sensitivities of 0.968, 1, and 0.939 and specificities of 0.956, 1, and 0.977 for skin, lipomas, and malignant tumors, respectively. Based on these results, we concluded that the proposed multimodal approach, combining Raman and OCT data, can accurately distinguish between malignant and benign tissues.

Utility of Serum Ki-67 as a Marker for Malignancy in Dogs.

Tumour markers are scarcely used in veterinary medicine, although they are non-invasive, contribute to a faster diagnosis and new therapeutic options. The nuclear protein Ki-67 is absent in G0-phase but is detectable throughout all active phases of the cell cycle. Consequently, it is used as a marker for the proliferating cell fraction of a cell population and thus could indicate neoplastic tissue present. Our study is designed to show whether Ki-67 can be considered as a potential canine serum tumour marker for veterinary medicine. We measured serum concentrations of Ki-67 in dogs with various malignant tumours (carcinomas (n = 35); sarcomas (n = 26); lymphomas (n = 21)) using a commercially available quantitative sandwich ELISA from mybiosource. Dogs with malignant tumours showed significantly higher serum Ki-67 concentrations compared to healthy dogs (n = 19) and non-neoplastic diseased dogs (n = 26). No significant difference in serum Ki-67 concentration was detected between carcinoma, sarcoma, and lymphoma, nor between mammary adenocarcinoma and adenoma. In our investigations we also included some inflammatory parameters measured in blood, such as neutrophils, lymphocytes, and monocytes, and gained mixed results. The results of our study suggest that Ki-67 may be useful as a potential serum tumour marker, providing information about the presence of malignancies in a dog.

A retrospective study of 101 dogs with oral melanoma treated with a weekly or biweekly 6 Gy × 6 radiotherapy protocol.

One radiotherapy (RT) protocol used for canine oral melanoma (OM) gives 36 Gy total, in six weekly or biweekly fractions (6 Gy × 6). This retrospective study characterizes oncologic outcomes for a relatively large group of dogs treated with this protocol and determines whether radiation dose intensity (weekly vs. biweekly) affected either progression-free or overall survival (PFS and OS). Dogs were included if 6 Gy × 6 was used to treat grossly evident OM, or if RT was used postoperatively in the subclinical disease setting. Kaplan-Meier statistics and Cox regression modelling were used to determine the predictive or prognostic value of mitotic count, bony lysis, World Health Organization (WHO) stage (I, II, III, or IV), using systemic anti-cancer therapies, tumour burden at the time of RT (macroscopic vs. subclinical), radiation dose intensity (weekly vs. biweekly), and treatment planning type (manual vs. computerized). The median PFS and OS times for all dogs (n = 101) were 171 and 232 days, respectively. On univariate analysis PFS and OS were significantly longer (p = <.05) with subclinical tumour burden, WHO stages I or II, and weekly irradiation. On multivariable analysis, only tumour stage remained significant; therefore, cases were grouped by WHO stage (I/II vs. III/IV). With low WHO stage (I/II), PFS and OS were longer when irradiating subclinical disease (PFS: risk ratio = 0.449, p = .032; OS: risk ratio = 0.422, p = .022); this was not true for high WHO stage (III/IV). When accounting for other factors, radiation dose intensity had no measurable impact on survival in either staging group.

Expression of LIN28A/B and Let-7 miRNAs in canine mammary carcinomas / Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos

LIN28 is a RNA-binding protein including two highly conserved homologous, LIN28A and LIN28B. Proto-oncogenes such as LIN28A and LIN28B are generally targeted by the let-7 miRNAs in different types of human cancers. Here, we determined the expression of LIN28A in canine mammary tumor samples and the LIN28/let-7 pathway in canine mammary cell lines. In those cell lines, we identified a functional LIN28/let-7 pathway which exhibited high expression of let-7 members and low expression of its targets, including LIN28A and LIN28B. However, the mammary carcinoma tissue samples showed a frequent expression of LIN28A being expressed mainly in the epithelial cells. No association was observed between LIN28A expression and histopathological classification and grade, TNM and survival time. Our results suggested a possible role of the LIN28A protein in the development of canine mammary carcinomas due to the high frequency observed in the tumor samples (28 of 32). The in vitro experiments suggested that the LIN28/let-7 pathway is active in the tumor cells evaluated. However, more studies are necessary to elucidate the exact role of LIN28/let-7 pathway in canine mammary carcinomas.

LIN28 é uma proteína de ligação ao RNA, com duas formas homólogas altamente conservadas, LIN28A e LIN28B. Os proto-oncogenes LIN28A e LIN28B são regulados pela família de miRNAs let-7 em diferentes tipos de cânceres em humanos. No presente trabalho, o objetivo foi determinar a expressão de LIN28A em amostras de tumor mamário de cadelas e a via LIN28/let-7 em linhagens celulares mamárias caninas. Nestas linhagens, através das técnicas de qPCR e RNAseq, foi identificado que a via LIN28/let-7 apresenta-se funcional, com alta expressão dos membros da família let-7 e baixa expressão de seus alvos, entre eles LIN28A e LIN28B. No entanto, as amostras de tecidos de carcinomas mamários caninos demonstraram expressão frequente de LIN28A, sendo observada principalmente em células epiteliais. Não foram observadas associações entre expressão de LIN28A com classificação e gradação histopatológicas, TNM e tempo de sobrevida. Nossos resultados sugerem uma possível relação da proteína LIN28A no desenvolvimento de carcinomas mamários caninos devido à alta frequência observada nas amostras tumorais (28 de 32). Os experimentos in vitro sugerem que a via LIN28/let-7 é ativa nas linhagens celulares caninas avaliadas. Entretanto, estudos funcionais ainda são necessários para elucidar a função exata da via LIN28/let-7 nos carcinomas mamários caninos.

Identification of new candidate biomarkers to support doxorubicin treatments in canine cancer patients.

BACKGROUND: Both human and veterinary cancer chemotherapy are undergoing a paradigm shift from a "one size fits all" approach to more personalized, patient-oriented treatment strategies. Personalized chemotherapy is dependent on the identification and validation of biomarkers that can predict treatment outcome and/or risk of toxicity. Many cytotoxic chemotherapy agents, including doxorubicin, base their mechanism of action by interaction with DNA and disruption of normal cellular processes. We developed a high-resolution/accurate-mass liquid chromatography-mass spectrometry DNA screening approach for monitoring doxorubicin-induced DNA modifications (adducts) in vitro and in vivo. We used, for the first time, a new strategy involving the use of isotope-labeled DNA, which greatly facilitates adduct discovery. The overall goal of this work was to identify doxorubicin-DNA adducts to be used as biomarkers to predict drug efficacy for use in veterinary oncology. RESULTS: We used our novel mass spectrometry approach to screen for adducts in purified DNA exposed to doxorubicin. This initial in vitro screening identified nine potential doxorubicin-DNA adduct masses, as well as an intense signal corresponding to DNA-intercalated doxorubicin. Two of the adduct masses, together with doxorubicin and its metabolite doxorubicinol, were subsequently detected in vivo in liver DNA extracted from mice exposed to doxorubicin. Finally, the presence of these adducts and analytes was explored in the DNA isolated from dogs undergoing treatment with doxorubicin. The previously identified nine DOX-DNA adducts were not detected in these preliminary three samples collected seven days post-treatment, however intercalated doxorubicin and doxorubicinol were detected. CONCLUSIONS: This work sets the stage for future evaluation of doxorubicin-DNA adducts and doxorubicin-related molecules as candidate biomarkers to personalize chemotherapy protocols for canine cancer patients. It demonstrates our ability to combine in one method the analysis of DNA adducts and DNA-intercalated doxorubicin and doxorubicinol. The last two analytes interestingly, were persistent in samples from canine patients undergoing doxorubicin chemotherapy seven days after treatment. The presence of doxorubicin in all samples suggests a role for it as a promising biomarker for use in veterinary chemotherapy. Future studies will involve the analysis of more samples from canine cancer patients to elucidate optimal timepoints for monitoring intercalated doxorubicin and doxorubicin-DNA adducts and the correlation of these markers with therapy outcome.

A High Intensity Focused Ultrasound System for Veterinary Oncology Applications.

BACKGROUND: Magnetic resonance-guided focused ultrasound surgery is an incisionless energy-based thermal method that is used for ablating tumors in the veterinary clinic. AIMS AND OBJECTIVES: In this article we describe a prototype of a veterinary system compatible with magnetic resonance imaging intended for small-to-medium-sized companion animals that was developed and tested in vivo in adult rabbits. METHODS: Real-time monitoring of the ablation during the experiment was possible with MR thermometry. Experiments involved thermal monitoring of sonications applied in the thigh of the rabbits. A 38-mm diameter transducer operating at 2.6 MHz was used with a 60-mm-focal length. The robotic system employed 3 linear axes and one angular axis. For this study, only X and Y axis were enabled. Due to the target size limitations, motion in Z and Θ was not needed. The functionality of the positioning device was evaluated by means of MR thermometry, demonstrating sufficient heating and accurate motion in both axes of operation. RESULTS: The postmortem findings confirm the ability of the system to induce thermal ablations in vivo in the absence of adverse effects. CONCLUSIONS: The device is a reliable and affordable solution for companion animal hospitals, offering and additional tool for the veterinary oncology society.