Successful post-incomplete resection management of gastrointestinal stromal tumor using imatinib based on adenosine triphosphate-based tumor sensitivity assay in a dog.

Gastrointestinal stromal tumors arising from gastric cardia are uncommon in dogs. A few studies have shown the effectiveness of tyrosine kinase inhibitors in the treatment of canine gastrointestinal stromal tumors, but no standardized protocols are currently available. An 11-year-old spayed female Maltese dog was diagnosed with a gastrointestinal stromal tumor using histopathological and immunohistochemical analyses. An adenosine triphosphate-based tumor chemosensitivity assay revealed that imatinib at lower concentrations had a stronger inhibitory effect than toceranib. Based on the results of the assay, the dog was treated with imatinib after surgery. After 28 mo of therapy, there was no recurrence of the tumor. Key clinical message: Adenosine triphosphate-based tumor chemosensitivity assays may help clinicians to select appropriate postoperative chemotherapeutic drugs for incompletely resected gastrointestinal stromal tumors in dogs.

Gestion réussie à la suite d'une résection incomplète d'une tumeur stromale gastro-intestinale à l'aide de l'imatinib basée sur un test de sensibilité tumorale à base d'adénosine triphosphate chez un chien. Les tumeurs stromales gastro-intestinales résultant du cardia gastrique sont rares chez le chien. Quelques études ont montré l'efficacité des inhibiteurs de la tyrosine kinase dans le traitement des tumeurs stromales gastrointestinales canines, mais aucun protocole standardisé n'est actuellement disponible. Une chienne maltaise stérilisée de 11 ans a reçu un diagnostic de tumeur stromale gastro-intestinale à l'aide d'analyses histopathologiques et immunohistochimiques. Un test de chimiosensibilité tumorale à base d'adénosine triphosphate a révélé que l'imatinib à des concentrations plus faibles avait un effet inhibiteur plus fort que le tocéranib. Sur la base des résultats du test, le chien a été traité avec de l'imatinib après l'opération. Après 28 mois de traitement, il n'y a eu aucune récidive de la tumeur.Message clinique clé :Les tests de chimiosensibilité tumorale à base d'adénosine triphosphate peuvent aider les cliniciens à sélectionner les médicaments chimiothérapeutiques postopératoires appropriés pour les tumeurs stromales gastro-intestinales incomplètement réséquées chez le chien.(Traduit par Dr Serge Messier).

Double-wire woven nitinol stent for treating dogs with refractory tracheal collapse: A case series.

This retrospective case series describes the signalments, clinical signs, diagnostic test results, and postoperative complications obtained from the medical records of 10 client-owned dogs that underwent treatment for grade IV tracheal collapse using double-wire woven nitinol stents between October 2017 and September 2021. Respiratory signs resolved in all dogs immediately after tracheal stent placement. Mild to moderate stent fractures were identified in five dogs, of which two showed concurrent respiratory distress necessitating re-stenting after several months. Minor complications, such as stent migration, were absent. The double-wire woven nitinol stent optimised for the canine trachea showed favourable outcomes and minimal complications.

Adjuvant therapy with toceranib for hepatocellular carcinoma and cholangiocarcinoma in a Pomeranian.

A 10-year-old spayed female Pomeranian dog was referred for hepatic mass evaluation. Blood tests revealed mildly elevated alkaline phosphatase activities. Computed tomography revealed a mass with multiple nodules on the right hepatic medial lobe adjacent to the caudal vena cava; histopathology confirmed mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Because of incomplete resection, adjuvant therapy was recommended. As tumour cells showed PDGFR-α, c-Kit, and FGFR1 overexpression, the anticancer effect of tyrosine kinase inhibitors was evaluated on the cells; toceranib was the most effective and was administered starting with an extra-labelled dose. The dog remained stable for 2.3 years with mild adverse effects. To our knowledge, this is the first successful clinical application of toceranib in a dog with mixed HCC-CC.

Long-term adjuvant metronomic chemotherapy in a dog with recurrent maxillofacial osteosarcoma.

Osteosarcoma (OSA) is the most common malignant bone tumour in dogs; however, OSA of the maxilla is uncommon compared to appendicular OSA. Oral melanoma also commonly occurs in dogs with frequent distant metastasis. The role of adjuvant chemotherapy has been questioned in maxillary OSA and melanoma. A 17-year-old English Cocker Spaniel was referred with a growing mass on the right maxilla and a right lower lip mass. Osteosarcoma was diagnosed after partial maxillectomy, and the right lower lip mass was diagnosed as oral melanoma. Metronomic chemotherapy (MC) was performed, and the number of doses was tapered due to side effects at 5 weeks after initiation of MC. After 130 weeks of MC, chemotherapy was suspended due to kidney disease. After the suspension of chemotherapy, findings suggesting recurrence and metastasis were detected. The dog suddenly died 193 weeks after surgery, which was 8-14 times longer than the expected survival time. To the best of our knowledge, this is the first case report of successful long-term combination therapy, including surgery and MC, in a dog with maxillary OSA and lip melanoma. Our results show that the survival time can be greatly extended if MC is performed with proper management.

Use of coccygeal vertebra autograft and platelet-rich plasma for treating a distal radial nonunion fracture in a small-breed dog.

A 4.3-kg, 11-month-old, spayed female poodle was presented for treatment of a right radio-ulnar nonunion fracture. Clinical history included failed surgical correction of a radius fracture with internal fixation 1 mo before presentation. Radiographic examination revealed a 1.5-cm lytic lesion on the right distal radius. Surgery was planned with a coccyx autograft and platelet-rich plasma. A 2.8-cm-long bone defect was created, and the lytic lesion was removed. Caudectomy was performed; the 6th and 7th coccygeal bones were harvested, placed into the defect, and fixed to the radius with a locking plate. Remnants of coccygeal bone were ground, mixed with platelet-rich plasma, and used to fill the bone defects. There was no evidence of nonunion or delayed union at the 18-month follow-up examination. Key clinical message: Based on the study findings, we inferred that a coccyx autograft and platelet-rich plasma can be used for successful reconstruction of a distal radial defect.

Utilisation d'une autogreffe de vertèbre coccygienne et de plasma riche en plaquettes pour le traitement d'une fracture radiale distale avec non-union chez un chien de petite race. Une femelle caniche stérilisée de 4,3 kg, âgée de 11 mois, a été présentée pour le traitement d'une fracture radio-ulnaire droite avec non-union. Les antécédents cliniques comprenaient l'échec de la correction chirurgicale d'une fracture du radius avec fixation interne 1 mois avant la présentation. L'examen radiographique a révélé une lésion lytique de 1,5 cm sur le radius distal droit. La chirurgie était prévue avec une autogreffe de coccyx et du plasma riche en plaquettes. Un défaut osseux de 2,8 cm de long a été créé et la lésion lytique a été retirée. Une caudectomie a été réalisée; les 6e et 7e os coccygiens ont été prélevés, placés dans le défaut et fixés au radius avec une plaque de verrouillage. Les restes d'os coccygien ont été broyés, mélangés avec du plasma riche en plaquettes et utilisés pour combler les défauts osseux. Il n'y avait aucune évidence de non-union ou de retard de consolidation lors de l'examen de suivi à 18 mois.Message clinique clé :Sur la base des résultats de l'étude, nous avons déduit qu'une autogreffe de coccyx et du plasma riche en plaquettes peuvent être utilisés pour une reconstruction réussie d'un défaut radial distal.(Traduit par Dr Serge Messier).

Different outcomes of multiple sialadenitis involving the submandibular and zygomatic salivary glands in a Welsh Corgi dog.

A ten-year-old indoor, castrated male Cardigan Welsh Corgi (Canis familiaris) presented with the chief complaints of chronic vomiting, retching, hypersalivation, and bilateral submandibular masses for two months. The systemic examinations, including serum chemistry, radiography, ultrasonography, and fluoroscopy, were unremarkable. A fine-needle aspiration revealed bilateral submandibular sialadenitis. Broad-spectrum antibiotics with phenobarbital were prescribed to alleviate the ptyalism. Thereafter, the left submandibular glands were normalised, and the right submandibular glands decreased to half their size. Three weeks later, the animal had an emergency visit because of a sudden left exophthalmos. Computed tomography and magnetic resonance imaging revealed enlarged left zygomatic and right mandibular salivary glands. The affected glands were surgically removed; the histopathologic examination confirmed non-septic sialadenitis, and the patient was finally diagnosed with idiopathic sialadenitis. Vomiting continued after the gland removal and the dog required a gradual increase in the phenobarbital dosage and an additional antiepileptic drug (potassium bromide) to manage the symptoms. The patient died eight months later from an unknown cause. This case report of bilateral submandibular sialadenitis concurrent with unilateral zygomatic sialadenitis in a Welsh Corgi dog suggests that when multiple salivary glands are involved, the response to anti-epileptic drugs and the prognosis is poor compared to that involving a single salivary gland.

Adjuvant therapy with imatinib for an incompletely resected multilobular tumour of bone in a dog.

A 5-year-old neutered male Shiba Inu dog presented with a history of oral bleeding, dysphagia, and depression for 3 weeks. The physical examination revealed a firm mass in the right caudal palatal region along the level of PM4-M2. On the computed tomography, the mass was round-to-oval in shape and 22 mm × 30 mm × 15 mm in size. The mass contained multiple bone attenuated materials with a palatal bone lysis of 4 mm × 6 mm. A complete resection of the mass was proposed; however, the owner declined due to the risk of complications associated with the radical surgery. Therefore, a palliative resection and biopsy of the mass were performed. On the histological examination, the mass was diagnosed as grade 2 multilobular tumour of bone (MTB). Since the mass was incompletely resected, adjuvant therapy was pursued along with targeted therapy using a tyrosine kinase inhibitor. The tumour cells showed overexpression of the receptor of tyrosine kinase for c-KIT, PDGFR-α, PDGFR-ß, and FGFR1 compared to normal tissue cells. Additionally, the cytotoxic effect of imatinib on the MTB cells was confirmed in vitro. Four weeks postoperatively, the administration of imatinib and carprofen was initiated and continued for 259 days. The patient maintained a good functional outcome for 306 days after the initial presentation.

Establishment of Canine Transitional Cell Carcinoma Cell Lines Harboring BRAF V595E Mutation as a Therapeutic Target.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract and tends to have a poor prognosis due to its invasive potential. Recent studies have reported that up to 80% of canine urothelial carcinoma has the BRAF V595E mutation, which is homologous to the human V600E mutation. Activating the BRAF mutation is an actionable target for developing effective therapeutic agents inhibiting the BRAF/mitogen-activated protein kinase (MAPK) pathway in canine cancer as well as human cancer. We established novel canine TCC cell lines from two tumor tissues and one metastatic lymph node of canine TCC patients harboring the BRAF V595E mutation. Tumor tissues highly expressed the BRAF mutant and phosphorylated extracellular signal-related kinases (ERK)1/2 proteins. The derived cell lines demonstrated activated MAPK pathways. We also evaluated the cell lines for sensitivity to BRAF inhibitors. Sorafenib, a multiple kinase inhibitor targeting RAF/vascular endothelial growth factor receptor (VEGFR), successfully inhibited the BRAF/MAPK pathway and induced apoptosis. The established canine TCC cell lines responded with greater sensitivity to sorafenib than to vemurafenib, which is known as a specific BRAF inhibitor in human cancer. Our results demonstrated that canine TCC cells showed different responses compared to human cancer with the BRAF V600E mutation. These cell lines would be valuable research materials to develop therapeutic strategies for canine TCC patients.

Surgical Reconstruction of the Metatarsal Pad Using Nonweight-Bearing Surfaces of the Footpads in a Dog.

A 9 yr old mixed-breed dog weighing 6.3 kg was presented with degloving injuries and multiple lacerations on the footpads of both hindlimbs. After amputation of the left hindlimb and debridement of the necrotic footpads on the right hindlimb, the remaining pads were insufficient for ambulation. The complete carpal pads and the peripheral, nonweight-bearing portions of the second and fifth digital pads of both forelimbs were harvested for pad grafting. All segments were sutured on the cutaneous trunci muscle in the predetermined location of the right abdominal wall for the pouch flap. After detaching the flap, the grafted segments were gradually strengthened, and the dog was able to regain ambulation. When considering pad grafting, the entire carpal pad and crescent-shaped segments from the nonweight-bearing surfaces of digital pads are excellent candidates for free grafts without compromising the ambulation of other limbs.

Parotid Duct Ectasia in a Dog.

A 3yr old spayed female Brittany was referred with a cylindrical mass on the right side of her face. Three months earlier, a small stone embedded in the right parotid duct was noted and removed through a ductal incision by the referring veterinarian. At referral, the dog's general physical condition was normal except for a cylindrical mass on the right cheek. Skull radiographs showed a possibly retained sialolith or dystrophic mineralization within the previous surgical site. Aspiration of the mass yielded a thick, yellow/tan, mucopurulent fluid. Cytology of the fluid demonstrated degenerative neutrophils without bacteria. The cylindrical mass was excised with a carbon dioxide laser. The caudal end of the mass was connected to the parotid salivary gland and the rostral one-third of the mass tapered to a point. The caudal end of the mass was ligated with 3-0 polydioxanone and excised immediately rostral to the ligation. Histopathology revealed that the mass was parotid duct ectasia. The dog completely recovered with some mild temporary facial paresis and had no recurrence of parotid duct ectasia at 4 mo follow-up. The case report describes a dog with an unusual parotid salivary duct ectasia caused by parotid duct sialolith removal.

Splenic malignant fibrous histiocytoma with concurrent hypertension and epistaxis in an Alaskan malamute dog.

BACKGROUND: Malignant fibrous histiocytoma has been uncommonly described in dogs. Several extranasal neoplasias have been reported to result hypertensive epistaxis. There are, however, no published case reports of extranasal malignant fibrous histiocytoma with concurrent hypertension and epistaxis in dogs. CASE PRESENTATION: A 10-year-old dog presented with a spontaneous massive epistaxis persisting for 5 days. The dog exhibited unstable hypertension, which was considered as a cause of epistaxis. The complete blood count, prothrombin time, and activated partial thromboplastin time were within the reference limits, and other systemic examination showed no abnormalities except for a splenic mass occupying more than one third of the abdomen. Histologic examination of the resected spleen revealed the characteristic features of a malignant fibrous histiocytoma. One week after splenectomy, the hypertension and epistaxis resolved clinically and did not recur on the 5-month follow-up. CONCLUSIONS: The dog's blood pressure and epistaxis normalized after malignant fibrous histiocytoma resection suggesting that hypertensive epistaxis may be a rare manifestation of canine malignant fibrous histiocytoma.

Ahmed glaucoma valve implantation with Ologen® Collagen Matrix for the surgical treatment of feline glaucoma.

An Ahmed valve implantation with an Ologen® Collagen Matrix (Ologen® CM, Aeon Astron, Leiden, the Netherlands) was performed for the treatment of uncontrolled glaucoma in a cat. This cat was a 5-year-old castrated Russian Blue male with a 12-week history of conjunctival hyperemia and mydriasis of the left eye. During the ophthalmic examination, the intraocular pressure (IOP) oculus sinister (OS) was 52 mmHg, and a narrow iridocorneal angle (ICA) was detected by gonioscopy. Medical treatment with Cosopt® (2% dorzolamide and 0.5% timolol) failed to decrease the IOP. The left eye still had vision, and an Ahmed valve implantation was performed. During the gonioimplantation, Ologen® CM was used to inhibit scar formation around the valve. Following the operation, the IOP was stable at an approximate average of 15 mmHg during the 7-month follow-up period, and vision in the left eye was retained without medication. An adequate subconjunctival filtering bleb was formed after 140 days. This is the first case report in which an Ahmed valve gonioimplant with an Ologen® CM has been used for the surgical treatment of glaucoma in a cat.

Successful management of lymphangiosarcoma in a puppy using a tyrosine kinase inhibitor.

A puppy was diagnosed with lymphangiosarcoma associated with lymphedema based on lymphography and histopathology. The lesions resolved after toceranib therapy, and the dog remains in remission 1 year later. This is the first report of a successful outcome following oral toceranib as first-line therapy for lymphangiosarcoma in a dog.

Gestion réussie d'un lymphangiosarcome chez un chiot à l'aide d'un inhibiteur de la tyrosinekinase. Un chiot a été diagnostiqué avec un lymphangiosarcome associé à un lymphoedème en se basant sur une lymphographie et l'histopathologie. Les lésions se sont résorbées après un traitement au tocéranib et le chien demeurait en rémission un an plus tard. Il s'agit du premier rapport d'un résultat favorable après le recours au tocéranib oral comme traitement de premier recours pour le lymphangiosarcome chez un chien.(Traduit par Isabelle Vallières).

Evaluation of the effects of topical zinc gluconate in wound healing.

OBJECTIVE: To evaluate the effects of topical zinc gluconate on healing, analgesia, and bacterial growth of full-thickness rat skin wounds. STUDY DESIGN: Experimental study. ANIMALS: Male Wistar rats (n = 98) METHODS: One full-thickness round 2 cm × 2 cm surgically created wound on the dorsum of each rat received 1 of the following randomized treatments: zinc gluconate in carrier solution, carrier solution, saline (0.9% NaCl) solution, chlorhexidine, chlorhexidine + zinc gluconate, corticosteroid, and no treatment. At 4 and 21 days, biopsy samples were taken for histopathology. Bacterial cultures were performed on day 4. Subjective pain scores and weight were recorded daily. RESULTS: No significant differences were noted among the groups except the corticosteroid group, in which delayed healing was noted at 4 and 21 days. Bacterial isolates were similar and no differences in pain scores or weight gain were noted among groups. The wounds treated with corticosteroid at day 4 had decreased inflammatory cells and serocellular crust formation, and minimal neovascularization and granulation tissue formation. At day 21, that group had prolonged neutrophilic inflammatory cells, immature fibrosis, less re-epithelialization, and more prominent serocellular crust. CONCLUSION: Wounds treated with zinc gluconate healed similarly and contained similar bacterial load as wounds with other topical treatments except for corticosteroids. No treatment demonstrated the negative effects seen with topical corticosteroid nor did any demonstrate analgesic advantage.

Primary cranial mediastinal hemangiosarcoma in a young dog.

Primary cranial mediastinal hemangiosarcomas are uncommon tumors. A 30-kg, 2-year-old, intact female German shepherd was presented for evaluation of cachexia and respiratory distress of a few days' duration. Lateral radiographic projection of the thorax revealed significant pleural effusion. Computed tomography revealed a cranial mediastinal mass effect adjacent to the heart. On surgical exploration, a pedunculated mass attached to the esophagus, trachea, brachiocephalic trunk, left subclavian artery and cranial vena cava without attachment to the right atrium and auricular appendage was removed and debrided by use of blunt dissection and dry gauzes, respectively. Histopathology results described the cranial mediastinal mass as hemangiosarcoma. At 8 months and 5 days post-operatively, the patient died. Primary cranial mediastinal hemangiosarcomas, although a seemingly rare cause of thoracic pathology in young dogs, should be considered in the differential diagnosis for pleural effusion and soft tissue mass effect in the cranial mediastinum. This is the first case report in a dog to describe primary cranial mediastinal hemangiosarcoma.

Fatigue analysis of canine tracheal stents using the finite element method.

This study aimed to evaluate fatigue of three stent designs when various forces are applied and perform a comparative analyses. A computer simulation using the finite element method was performed. In particular, we constructed a three-dimensional finite element model of nitinol stents with three designs (S6: single-woven wire, wire diameter: 0.006 inch; D6: double-woven wire, wire diameter: 0.006 inch, and D7: double-woven wire, wire diameter: 0.007 inch) that are used to treat canine tracheal collapse (TC). The stents were subjected to a 200 mmHg compression force, a pure torsion force in a perpendicular direction, and a bending-torsion force combining perpendicular and axial forces. The von Mises stress was calculated to evaluate the extent of stent displacement, and Goodman diagrams were plotted to compare fatigue life cycles. D7 exhibited a longer fatigue life compared to S6 and D6. Under compression, pure torsion, and bending-torsion forces, displacement was the smallest for D7, followed by D6 and S6. Similarly, the fatigue life was the longest for D7, followed by D6 and S6. S6 showed the greatest displacement when subjected to external forces; among stents designed using the same wire, D6 displayed less displacement than S6, and D7 exhibited superior fatigue life when subjected to varying degrees of force. This study showed that the structural stability and fatigue life of stents could be effectively compared using finite element method D7 has the greatest stability and structural rigidity under cyclic load.

Clinical evaluation and surgical intervention for diaphragmatic eventration mimicking peritoneopericardial hernia in a cat.

A 2-year-old spayed female British Shorthair cat presented with an increased frequency and duration of cough since infant period. Based on radiographic, ultrasonographic, and computed tomography findings, peritoneopericardial diaphragmatic hernia was considered so that repair surgery was planned. During celiotomy, lax diaphragm was identified instead of defect. Transabdominal diaphragmatic plication was performed to resolve lax diaphragm and to prevent recurrence by overlapping relatively normal part of diaphragm. Diagnosed with diaphragmatic eventration postoperatively, the cat showed improvement in clinical signs and imaging results. Transabdominal diaphragmatic plication is a suitable treatment; the patient maintained normally during a 14-month follow-up period.

Reconstructive surgery with an autologous bone graft in a dog with presumptive chronic non-bacterial osteomyelitis.

A 15-year-old Cocker Spaniel was referred to for the evaluation of left forelimb lameness. Radiographic and computed tomography examinations revealed osteolysis of the proximal left third, fourth and fifth metacarpal bones and pathological fractures of the proximal left fourth metacarpal bone. Histopathological examination via bone biopsy did not provide a definitive diagnosis, and the owner elected limb-sparing surgery. The fourth metacarpal bone and digits were amputated. Subsequently, autologous bone grafts were performed on the lytic area of the third and fifth metacarpal bones. The dog showed improvement in gait 7 weeks after reconstructive surgery. Chronic non-bacterial osteomyelitis (CNO) was diagnosed by exclusion. To the best of our knowledge, CNO has not been previously reported in dogs.

Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

IMPORTANCE: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). OBJECTIVE: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. METHODS: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 106 cells, group C with 3 × 106 cells, group D with 1 × 106 cells, group E with 1 × 106 cells injected twice with a one-day interval, group F with 2 × 106 cells in 100 µL of suspension, and group G with 2 × 106 cells in 300 µL of suspension. RESULTS: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). CONCLUSIONS AND RELEVANCE: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

Establishment and characterization of six canine hepatocellular carcinoma cell lines.

Background: Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in dogs. Although surgical resection is a major treatment option for canine HCC, there are no distinct strategies for unresectable tumor subtypes or adjuvant chemotherapy for tumors with positive margins. We aimed to establish and characterize novel HCC cell lines from canine patients. Methods: The cellular morphology, general growth features and tumorigenicity of the established cell lines were evaluated. We also examined the sensitivity of the cell lines to multi-target tyrosine kinase inhibitors (TKIs). Results: We established novel canine HCC cell lines from hepatic tumors and an additional kidney tumor of six canine patients. All cell lines showed colony forming and migratory ability. KU-cHCC-001 and KU-cHCC-001-Kidney, two cell lines exhibiting high epithelial-mesenchymal transition characteristics, showed tumorigenicity in xenografted mice. Toceranib, a veterinary TKI that targets vascular endothelial growth factor (VEGFR)/platelet-derived growth factor receptor (PDGFR)/c-kit, effectively inhibited the mitogen-activated protein kinase pathway and induced apoptosis. The established canine HCC cell lines showed greater sensitivity to toceranib than to sorafenib, a first-line treatment for human HCC targeting RAF/VEGFR/PDGFR. Sorafenib showed improved anti-tumor effects when co-treated with SCH772984, an extracellular signal-regulated kinase inhibitor. Conclusion: Our study suggests new therapeutic strategies for canine HCC, and these cell lines are valuable research materials for understanding HCC tumor biology in both humans and dogs.