Veterinary Oncology Research Articles

The cyclooxygenase-2/prostaglandin E2 pathway and its role in the pathogenesis of human and dog hematological malignancies.

The overexpression of cyclooxygenase-2 (COX-2) has been documented in many types of cancer occurring in humans and animals. Increasing evidences have shown that the overexpression of COX-2 and increased production of prostaglandin E2 (PGE2) correlate with poor prognosis in human solid tumours and hematological malignancies. Both, in vitro and in vivo studies have demonstrated that increased proliferation of cancer cells as well as an impairment of anti-tumour immunity are influenced by the overexpression of this enzyme. In leukemia and lymphoma, an increased activity of COX-2 and subsequent increase in prostaglandins (PGs) concentration allow cancer cells to evade immune response and contribute to metastases. Cancer stem cells (CSCs) in tumour microenvironment, suppression of innate and adaptive immunity depends on COX-2/PGE22 axis activity which increases in hematological malignancies. Cyclooxygenases inhibitors block the formation of PGs, consequently inhibiting angiogenesis, and in some malignancies they decrease cancer cells proliferation and tumour invasiveness. They also increase apoptosis of CSCs and cancer cells, decrease their drug resistance as well as enhance the host immune response. Therefore COX-2/PGE2 axis suppressors: selective COX-2 inhibitors or PG receptors antagonists have been considered as promising anticancer drugs. In comparative oncology dogs are increasingly used as a large animal model because they share the same environmental conditions with people and are exposed to the same environmental factors and also due to their relatively short life span. In dogs, spontaneously occurring non-Hodgkin lymphomas and leukemias have a large number of genetic and morphological features that are similar to those of humans' corresponding cancers. This, additionally makes the species a useful model for the study of new therapeutic strategies in human oncology. While the influence of COX-2 activity and PGE2 receptors have been evaluated extensively in human cancer, their role in veterinary oncology still needs to be elucidated.

Clinical Evaluation of Glycoproteins and Inflammatory Cytokines in the Serum of Dogs Affected with Canine Mammary Cancer

In canine mammary tumours, role of surface glycoproteins and cytokines is poorly understood as focus on these markers in the veterinary practice is lacking. The serum markers in 41 malignant CMT cases along with six control dogs were studied to determine their importance in the diagnosis and prognosis of CMT. The surface glycoproteins (CA 15.3 and CEA) and inflammatory cytokines (IL-8 and TNF-α) in mammary tumour cases were significantly higher than those of controls. The Kaplan–Meier survival analysis elucidated poor survival in cases with high serum marker levels. The studies implicate that serum glycoproteins and cytokines are important determinants of diagnosis and prognosis of this tumour having great relevance in veterinary oncology.

Haemangiopericytomas in dogs: Epidemiological analysis of 136 cases

Perivascular wall tumors (PWTs or haemangiopericytomas) are common in dogs, and they are clinically important in veterinary oncology, but there is no data on the occurrence of these tumors in dogs in Poland. The aim of the present study was an epidemiological analysis of canine perivascular wall tumors. The study included 136 dogs with recognized PWTs (whose frequency of occurrence was the same in females and males). The mean age of the dogs was 9.8±3.0 years, with no statistically significant difference between sexes. Among the dogs, 40.7% were mongrels, and 59.3% were purebred. Among the purebred dogs, 21 (26.3%) were German Shepherds, 17 (21.3%) were Boxers, 5 (6.3%) were Doberman pinchers and Rottweilers. Statistical analysis revealed that four breeds were predisposed to perivascular wall tumors in comparison to the general dog population: German Shepherds, Boxers, Doberman pinchers and Rottweilers. Moreover, large-breed (but not giant-breed) dogs were shown to be predisposed to PWTs. Tumors were located in the skin or subcutis of the entire body, mostly on the legs, more seldom on the trunk or the head. The most typical location for PWTs was the elbow area (11% of all cases).

Low frequency of pre-treatment and post-treatment haematological abnormalities in dogs with non-infectious meningoencephalitis treated with cytosine arabinoside and prednisolone

BackgroundCytosine arabinoside (CA) and prednisolone are drugs commonly used together in the management of canine non-infectious meningoencephalitis (NIME). The aim of this study was to report the haematological findings before...

MicroRNA and cancer: a focus on mammary tumors in female dogs

ABSTRACT: Mammary tumors are the most frequent tumors reported in female dogs and have great relevance in veterinary oncology; however, little is known about the molecular mechanisms involved in the development of metastasis. An increasing number of human studies have suggested that epigenetic alterations, such as DNA methylation, miRNA, and histone modifications, are the predominant events leading to the metastatic phenotype in tumor cells and participate in regulating oncogenic signals associated with tumor spread. Among these epigenetic alterations, miRNAs have stood out in recent years, presenting a fundamental role in tumorigenesis. There are still few studies evaluating the role of miRNAs in canine mammary tissues. Thus, this paper aims to review the role of miRNAs in cancer with a special focus on canine mammary tumors.

Canine Cancer Genomics: Lessons for Canine and Human Health.

Dogs are second only to humans in medical surveillance and preventative health care, leading to a recent perception of increased cancer incidence. Scientific priorities in veterinary oncology have thus shifted, with a demand for cancer genetic screens, better diagnostics, and more effective therapies. Most dog breeds came into existence within the last 300 years, and many are derived from small numbers of founders. Each has undergone strong artificial selection, in which dog fanciers selected for many traits, including body size, fur type, color, skull shape, and behavior, to create novel breeds. The adoption of the breed barrier rule-no dog may become a registered member of a breed unless both its dam and its sire are registered members-ensures a relatively closed genetic pool within each breed. As a result, there is strong phenotypic homogeneity within breeds but extraordinary phenotypic variation between breeds. One consequence of this is the high level of breed-associated genetic disease. We and others have taken advantage of this to identify genes for a large number of canine maladies for which mouse models do not exist, particularly with regard to cancer.

Autologous canine immunotherapy: short-time generated dendritic cells loaded with canine transmissible venereal tumor-whole lysate

Objective: The aim of the present study was to evaluate the therapeutic potential of autologous DCs loaded with whole tumor cell lysate of CTVT generated under a simplified and rapid procedure in vitro production process, in a vulvar submucosal model of CTVT in dogs.Materials and methods: We generated a model of intravulvar CTVT in dogs. A CTVT lysate antigen was prepared according to the method of 1-butanol and after administered with complete Freund's adjuvant via subcutaneous in female healthy dogs and challenge with CTVT cells to corroborate the immunogenicity. Short-time generated dendritic cell pulsed with CTVT whole-lysate was performed, and analyzed by FITC-dextran uptake assay and characterized using anti-canine monoclonal antibodies CD14, CD80, CD83, and DLAII by flow cytometry. Dendritic cell therapy was administered in a frequency of three times every 2 weeks when the CTVT had 4 months of growth and 89 ± 5 cm diameter. The CD3+, CD4+ and CD8+ lymphocytes were determined by flow cytometry, and IFN-γ by ELISA assay.Results and discussion: The administration of CTVT whole-lysate resulted in tumor prevention. The short-time generated dendritic cell pulsed with CTVT whole-lysate administration resulted in an efficient reduction and elimination of CTVT, probably due to the increase in lymphocyte populations (CD3+, CD4+, and CD8+), IFN-γ production and tumor infiltrating lymphocytes.Conclusion: In conclusion, this study demonstrates the efficacy of immunotherapy based in short-time generated dendritic cell pulsed with CTVT whole-lysate for the treatment of CTVT, and offer veterinary oncologists new alternative therapies to treat this and another malignancy.

Concurrent 5-fluorouracil and carboplatin for the treatment of canine carcinomas.

5-Fluorouracil (5-FU) is used in combination chemotherapy protocols for human head and neck cancer and other epithelial neoplasms. However, a paucity of literature describing use of this drug in veterinary oncology exists, likely due to previous reports of fatal neurotoxicity in both dogs and cats, mainly due to ingestion of human creams. The primary aim of this retrospective study was to report the safety of concurrent 5-FU and carboplatin in canine carcinomas. Secondarily, we aimed to look at the efficacy of the combination using overall response rate in treated dogs. Medical records were searched from 2007 to 2017 for dogs treated with both agents; 24 dogs met inclusion criteria. Carboplatin dosages ranged from 180 to 250 mg/m2 (median 200 mg/m2 ); 5-FU dosage was 150 mg/m2 . Fourteen dogs had myelosuppression, ranging from Grade I to asymptomatic Grade IV; thrombocytopenia was more common than neutropenia. Gastrointestinal upset was uncommon, with only seven dogs having Grade I or II nausea, vomiting or diarrhoea. No cases were hospitalized for any of the above toxicities. One dog had an episode of ataxia, which could not be differentiated between otitis and 5-FU neurotoxicity. This protocol is well tolerated. Response rate in the gross disease setting was 43% (three complete responses, three partial responses). Prospective analysis of this combination protocol, and potentially 5-FU with other platinum agents, is warranted in the treatment of canine carcinomas.

The future of radiotherapy in small animals – should the fractions be coarse or fine?

Radiation therapy has been used to treat animal cancers for more than 100 years. Clinical experiences and experimental results have been widely published and provide a basis for the recognition of radiation therapy as an integral component of multimodal cancer management in veterinary oncology. As the expectations of pet owners and the demand for treatment of companion animals with cancer have increased, veterinary oncology itself has undergone dramatic advances in the past several decades both in terms of improved diagnostics and treatments, including increased accessibility of radiation therapy. Synchronous with development of the specialism of veterinary radiation oncology, confusion and controversy have arisen with regard to distinguishing between different types of radiotherapy and methods of treatment delivery. Importantly, the confusion extends beyond semantics, and includes opinionated debate about defining which forms of therapy (if any at all) are optimal for a given patient. This exemplifies how, despite marks of maturity including age and a robust publication history, the field of veterinary radiation oncology is in some ways still in its infancy. The purpose of this article is to review the evidence base for daily (fine) fractionation versus weekly (coarse) hypofractionation in veterinary oncology, using selected tumour types as examples.

Diferential Diagnosis between Esophageal Granuloma and Pulmonary Metastasis

Background: Spirocercosis is a parasitic infection caused by Spirocerca lupi. This pathology affects canid carnivores, especially domestic dogs. Early diagnosis has been proven challenging and most infected animals are diagnosed when disease is in advanced stage. Exams such as computed tomography scans or radiographs can aid in disease confirmation.Radiographic exam frequently reveals the presence of a mass located in mediastinal region, which can be erroneously diagnosed as pulmonary mass. The aim of this study was to report the differential diagnosis between paraesophageal granuloma, possibly due to spirocercosis, and pulmonary metastasis in a dog with a history of neurofibrosarcoma.Case: A 8 year-old male Cocker Spaniel dog, weighing 17.4 kg, was presented with anterior limb suspension and a recurrent nodule of 2.0 cm diameter, located on the main pad, with previous diagnosis of neurofibrosarcoma (malignant Schwannoma). Routine evaluation work-up included thoracic radiographs and abdominal ultrasound for clinical staging, electrocardiogram, complete blood count (CBC), coagulogram, renal and hepatic function tests, with results within the normal range for the species. The dog submitted to left anterior limb amputation due to recurrent neurofibrosarcoma in the carpal region. Histopathological exam confirmed recurrent neurofibrosarcoma without vascular invasion. Considering neoplasm biological behavior and clean surgical margins, only routine follow-up was established, with clinical exams. The dogwas presented to the Veterinary Hospital five months after surgical treatment and it was presented with fever, prostration, and history of vomiting. Radiographic exam showed a circumscribed mass in caudal mediastinal area. Computed tomography scan was performed to best evaluate the mass and the result was compatible with paraesophageal abscess. These findings were consistent with paraesophageal abscess with necrotic center caused by Spirocerca lupi; however, it was not possible to exclude the possibility of lymph node neoplasms, with necrotic center/secondary abscess. Coproparasitological test result was negative; however, considering the endemic aspect of spirocercosis, the dog was treated with Ivermectin was given orally, for 14 days, and complete remission was observed at the end of the treatment, without any significant side effects.Discussion: Spirocercosis has a worldwide dissemination, limited only by the presence of intermediate host. In endemic regions, prevalence in dogs may be 100%. Diagnosis may be challenging, especially in atypical cases and in patients with complications. Spirocercosis diagnosis may be achieved from therapeutic response in typical cases, with suggestiveradiographic and tomographic findings. Radiologic and tomographic findings in this case were similar to common spirocercosis findings. Follow up by a veterinary oncologist is of utmost importance; an unprepared veterinarian could indicate thoracotomy or even euthanasia. Even though coproparasitological exam was negative, the endemic aspect of spirocercosis in the area supported the decision for treatment and therapeutic diagnosis. Oncologic patients should be carefully evaluated,for not all pathologies they develop after a neoplasm diagnosis are related to cancer. Knowledge of disease biologic behavior is essential to make correct decisions regarding patient health status.Keywords: Spirocerca lupi, granulomas, neurofibrosarcoma.

Antibiotic prophylaxis in veterinary cancer chemotherapy: A review and recommendations.

Bacterial infection following cancer chemotherapy-induced neutropenia is a serious cause of morbidity and mortality in human and veterinary patients. Antimicrobial prophylaxis is controversial in the human oncology field, as any decreased incidence in bacterial infections is countered by patient adverse effects and increased antimicrobial resistance. Comprehensive guidelines exist to aid human oncologists in prescribing antimicrobial prophylaxis but similar recommendations are not available in veterinary literature. As the veterinarian's role in antimicrobial stewardship is increasingly emphasized, it is vital that veterinary oncologists implement appropriate antimicrobial use. By considering the available human and veterinary literature we present an overview of current clinical practices and are able to suggest recommendations for prophylactic antimicrobial use in veterinary cancer chemotherapy patients.

A single dose of intravenous combretastatin A4-phosphate is reasonably well tolerated and significantly reduces tumour vascularization in canine spontaneous cancers.

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).

Retrospective Study of Adverse Events of Chemotherapy in Cats

Background: Clients who seek veterinary care for pets with cancer are often concerned about the potential negative impact of chemotherapeutic treatments on their animals’ quality of life. A consensus currently exists in veterinary oncology regarding the quantification and rating of adverse treatment effects in dogs and cats in response to chemotherapy agents. This grading system is referred to as Veterinary Cooperative Oncology Group - Common Terminology Criteria for Adverse Events. The purpose of this retrospective case series was to investigate the delayed acute effects of chemotherapy drugs in cats receiving cancer treatment.Materials, Methods & Results: Medical records were reviewed to determine the chemotherapy agent used and delayed adverse effects. Side effects were classified according to Veterinary Co-operative Oncology Group grading. All cats were evaluated after the first chemotherapy administration, after a single dose. The reported effects included hematologic effects (e.g., neutropenia, thrombocytopenia, increases in liver enzymes, and azotemia), gastrointestinal effects (e.g., vomiting, diarrhea, and inappetence), and sepsis. All of the cats in this study received ondansetron and omeprazol in the first five days following chemotherapy administration. If vomiting occurred with oral medication, maropitant was administered subcutaneously for three consecutive days. If diarrhea (> grade II) occurred, probiotics were administered for seven days. Hematologic examination was performed 3-14 days after chemotherapy. If neutropenia (> grade III) occurred, Human granulocyte colony stimulating factor was administered subcutaneously for three consecutive days together with prophylactic antibiotics. Lomustine, carboplatin, vincristine, doxorubicin, cyclophosphamide, mitoxantrone, and vinblastine were administered in 33%, 19%, 16%, 5%, 16%, 10% and 2% of the cases examined, respectively. The most common adverse events were vomiting, inappetence, neutropenia, and thrombocytopenia. Vomiting occurred in 6% cases, most of them associated with cyclophosphamide. Inappetence/anorexia affected 12% of the cases, mostly those involving cyclophosphamide or doxorubicin. Neutropenia was observed in 22% of the cases, with cyclophosphamide, followed by carboplatin and lomustine. According to the current grading system of adverse effects induced by chemotherapy, grade I toxicity was observed in 83% of the cases, whiles grade II-IV were observed in 7%, 8%, and 2% of the cases examined, respectively.Discussion: In general, the chemotherapy regimens in the cases examined were well tolerated. The toxicity experienced was infrequent and mostly mild, thereby resulting in satisfactory tolerability of the chemotherapy regimens. According to the current grading system for the adverse effects of chemotherapy, 83% of the cases examined included grade I, indicating that most of the cats experienced asymptomatic, or mild symptoms, and medical intervention was not needed. In previous studies of dogs and cats, a severe adverse event following chemotherapy was reported for fewer than 1 in 4 animals, and approximately 3-5% experienced a serious adverse event that led to hospitalization. In the present study, 2% of the cats experienced serious or life threatening adverse events. The only chemotherapeutic agent that was associated with inappetence, vomiting, and neutropenia was cyclophosphamide. Based on the data examined, we would recommend that cyclophosphamide should be used with caution for the treatment of cancer in cats, with adequate antiemetic and nutritional support available if needed. In addition, febrile neutropenia/sepsis may be avoided by using a fractionated schedule.

A geriatria canina e o manejo das doenças neoplásicas: Revisão

Some changes in population habits have had an important impact on pet care. A greater approximation of owner-animal is observed, which has made dogs and cats incorporated into the family. In the same way, Veterinary Medicine has been developing in the most different areas, and veterinary oncology has been emphasizing with the new approaches. Neoplasms, in general, exhibit considerable variation in their semiologic, clinical and histological aspects and for these reasons, predictions of tumor behavior and responses to treatment may be extremely difficult and subjective. The fact that the dogs are reaching the greater age has predisposed to the appearance of these diseases with more frequency, being possible the study of these etiologies with more detail. Therefore, this review seeks to deepen questions related to canine geriatrics and the consequences of the greater age of dogs with the appearance of neoplasms. The relevant aspects on the etiology of neoplasms, their main complications and their management will be approached, considering the new therapies adopted today, as well as the observed relationship between the owners and their pets.

Antitumor effect of antibiotic resistance gene-free plasmids encoding interleukin-12 in canine melanoma model

The electrotransfer of interleukin-12 (IL-12) has been demonstrated as an efficient and safe treatment for tumors in veterinary oncology. However, the plasmids used encode human or feline IL-12 and harbor the gene for antibiotic resistance. Therefore, our aim was to construct plasmids encoding canine IL-12 without the antibiotic resistance genes driven by two different promoters: constitutive and fibroblast-specific. The results obtained in vitro in different cell lines showed that following gene electrotransfer, the newly constructed plasmids had cytotoxicity and expression profiles comparable to plasmids with antibiotic resistance genes. Additionally, in vivo studies showed a statistically significant prolonged tumor growth delay of CMeC-1 tumors compared to control vehicle-treated mice after intratumoral gene electrotransfer. Besides the higher gene expression obtained by plasmids with constitutive promoters, the main difference between both plasmids was in the distribution of the transgene expression. Namely, after gene electrotransfer, plasmids with constitutive promoters showed an increase of serum IL-12, whereas the gene expression of IL-12, encoded by plasmids with fibroblast-specific promoters, was restricted to the tumor. Furthermore, after the gene electrotransfer of plasmids with constitutive promoters, granzyme B-positive cells were detected in the tumor and spleen, indicating a systemic effect of the therapy. Therefore, plasmids with different promoters present valuable tools for focused therapy with local or systemic effects. The results of the present study demonstrated that plasmids encoding canine IL-12 under constitutive and fibroblast-specific promoters without the gene for antibiotic resistance provide feasible tools for controlled gene delivery that could be used for the treatment of client-owned dogs.

Engineering controls in veterinary oncology: A survey of 148 ACVIM board-certified oncologists and environmental surveillance in 20 specialty hospitals.

Engineering controls (EC, facility and equipment barriers between hazards and people) are used to avoid exposure to chemotherapy drugs. In this study, American College of Veterinary Internal Medicine board-certified veterinary oncologists were surveyed about their use of containment primary EC (C-PEC) and supplemental EC (closed system transfer devices, CSTD). The survey was completed by 148 (38%) of practicing diplomates. All used EC. Both C-PEC and CSTD were used at 92% of hospitals; however, US Pharmacopoeial Convention Chapter <800> (USP <800>) standards were met at only 19% of hospitals and oncologists did not know the type of C-PEC at 18% of hospitals. Next, surface contamination and EC use were assessed with environmental surveillance for carboplatin, cyclophosphamide, doxorubicin, and vincristine in 20 veterinary specialty hospitals using a commercially available kit. No contamination with carboplatin, doxorubicin, or vincristine was detected, however, there was contamination with cyclophosphamide at 4 hospitals. Based on this study, most veterinary oncologists use C-PEC and CSTD, but few meet USP <800> standards. Current measures appear effective for preventing contamination with IV drugs, but additional measures are needed for oral drugs.

BRAZILIAN CONSENSUS FOR THE DIAGNOSIS, TREATMENT AND PROGNOSIS OF CUTANEOUS MAST CELL TUMORS IN DOGS

Mast cell tumors represent the most common malignant skin tumor in the dog. This review outlines the incidence, etiology and clinical signs of mast cell tumors. Diagnostic tests, staging and treatments are also discussed. This study was performed by the Veterinary Oncology and Pathology of UNESP, Jaboticabal and the Service of Pathology Veterinary, of UNESP-Botucatu with the support of the Brazilian Association of Veterinary Oncology and the Brazilian Association of Veterinary Pathology.

Oestrogen receptors and antioestrogen treatment of hormone-dependent tumours

The oestrogen receptor is a ligand-activated transcription factor that modulates specific gene expression by binding to short DNA sequences. The study of the role of oestrogen receptor on the expression of the mitogenic actionof oestrogens and oncogenesis lead biomedical research in new approaches of the treatment of oestrogen-dependent tumors by using antioestrogens. Main mechanism of action of antioestrogens is the prevention of oestrogen action by blocking the binding of oestradiol to the oestrogen receptor. Tamoxifen, the most wellknown antioestrogen, is widely used as adjuvant therapy in all stages of human breast cancer. Recently interest is focused on the potential use of "pure" antioestrogens. The use of antioestrogens in veterinary oncology is also under discussion.

Interobserver reliability of computed tomographic contouring of canine tonsils in radiation therapy treatment planning.

In radiation therapy (RT) treatment planning for canine head and neck cancer, the tonsils may be included as part of the treated volume. Delineation of tonsils on computed tomography (CT) scans is difficult. Error or uncertainty in the volume and location of contoured structures may result in treatment failure. The purpose of this prospective, observer agreement study was to assess the interobserver agreement of tonsillar contouring by two groups of trained observers. Thirty dogs undergoing pre- and post-contrast CT studies of the head were included. After the pre- and postcontrast CT scans, the tonsils were identified via direct visualization, barium paste was applied bilaterally to the visible tonsils, and a third CT scan was acquired. Data from each of the three CT scans were registered in an RT treatment planning system. Two groups of observers (one veterinary radiologist and one veterinary radiation oncologist in each group) contoured bilateral tonsils by consensus, obtaining three sets of contours. Tonsil volume and location data were obtained from both groups. The contour volumes and locations were compared between groups using mixed (fixed and random effect) linear models. There was no significant difference between each group's contours in terms of three-dimensional coordinates. However there was a significant difference between each group's contours in terms of the tonsillar volume (P<0.0001). Pre- and postcontrast CT can be used to identify the location of canine tonsils with reasonable agreement between trained observers. Discrepancy in tonsillar volume between groups of trained observers may affect RT treatment outcome.

Flavopiridol Strongly Sensitizes Canine Lymphoma Cells to TRAIL-induced Apoptosis.

Targeting the extrinsic apoptotic pathway is an interesting option for anticancer therapy. A protein which such ability is Apo2 ligand, also known as TNF-related apoptosis-inducing ligand (TRAIL). The aim of this study was to examine the possibility of sensitizing resistant CLBL-1 canine lymphoma cells to TRAIL-induced apoptosis by using flavopiridol (FVP) a cyclin-dependent kinase inhibitor (CDKs). The CLBL-1 (canine B-cell lymphoma cell line) was used in the study. The effect of FVP and TRAIL treatment on apoptosis induction was assessed by flow cytometry and western blot. Although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cells. Our results demonstrated that although canine lymphoma cells were resistant to TRAIL-induced apoptosis, combination of this death ligand with FVP was able to overcome TRAIL resistance of CLBL-1 lymphoma cell line. Although further investigation is required to deepen the knowledge of TRAIL as an antitumor agent in canine cancers, our results open the door to future use of TRAIL-based treatment strategies in veterinary oncology.