• Journal of Veterinary Clinics
• /
• v.34 no.1
• /
• pp.43-46
• /
• 2017

A 10-year-old, spayed, female Cocker Spaniel was referred to our hospital with a history of a cough and dyspnea. The patient was tentatively diagnosed with a chemodectoma based on clinical features evident on echocardiography and computed tomography. Metronomic chemotherapy utilizing toceranib phosphate as well as medications for congestive heart failure were administered. During the period chemotherapy was administered (nine months from the time of diagnosis), clinical improvement was noted without the development of any adverse effects. However, clinical signs recurred after chemotherapy was discontinued at the owner's request. When the patient was reevaluated via computed tomography, it was found that the size of the mass had increased. The patient developed severe dyspnea secondary to recurrent pleural effusion and was euthanized 65 days after clinical signs reappeared. A necropsy was performed and the patient was definitively diagnosed with a chemodectoma based on histopathologic and immunohistochemical analysis. This case report describes the clinical application of metronomic chemotherapy with toceranib phosphate, which is a tyrosine kinase inhibitor, in the treatment of a chemodectoma. We propose that this treatment may improve the quality of life and result in a prolonged survival time compared to treatment with medications for congestive heart failure alone.

• Journal of Veterinary Clinics
• /
• v.40 no.6
• /
• pp.445-451
• /
• 2023

An 8-year-old female pet rabbit presented at the veterinary clinic for mammary gland palpation due to the presence of a mass. Upon physical examination, a mass was identified in the left fourth mammary gland. Abdominal ultrasonography revealed a 3 × 2 cm mass in the right uterus and general thickening of the endometrium, suggesting uterine sinusitis. Multiple pulmonary nodules suspected to be metastatic lesions were identified on chest radiography. Surgery was performed to mastectomy and ovariohysterectomy (OHE). The histopathological examination of the tumor revealed mammary gland adenocarcinoma (simple-type) with multiple nodules consisting of the proliferation of tumor cells forming tubules containing secretory materials, cellular debris, and solid nests with a central area of necrosis. Metronomic chemotherapy was performed with cyclophosphamide and lomustine (CCNU) based on the histopathological findings. The quality of life has been well maintained, with no specific clinical symptoms observed for 8 months after metronomic chemotherapy. To the best of authors' knowledge, this study is the first to examine the effects of metronomic chemotherapy with cyclophosphamide and lomustine in a pet rabbit.

• Journal of Veterinary Clinics
• /
• v.32 no.2
• /
• pp.183-186
• /
• 2015

A four-year-old spayed female Maltese dog weighing 3 kg was referred with reverse sneezing and fourmonth history of unilateral nasal discharge. She was diagnosed as nasal transitional carcinoma which in bilateral nasal cavity and extending into the frontal sinus by biopsy with rhinoscopy. Metronomic chemotherapy with cyclophosphamide ($12.5mg/m^2$) and toceranib phosphate (2.5 mg/kg) was initiated following after surgical treatment of nasal mass debulking. Clinical response was good and had no side effects during the chemotherapy period (11 months after diagnosis). This is a case report describing adjuvant metronomic chemotherapy in nasal transitional carcinoma in Korea.

• Journal of Veterinary Clinics
• /
• v.34 no.6
• /
• pp.441-444
• /
• 2017

A 15-year-old spayed female Miniature Schnauzer was presented for unilateral foreleg lameness and pain. On physical examination, left elbow joint swelling and stiffness were identified. On a computed tomography (CT) scan, a periosteal reaction of the left humerus from the distal metaphysis to the epiphysis and cortical destruction of the medial condyle was observed. Based on blood tests, histopathology, and immunohistochemistry, it was concluded as a skeletal histiocytic sarcoma. Since the patient's pain was not controlled despite application of a fentanyl patch, a left forelimb amputation was decided upon as part of the palliative therapy. Metronomic chemotherapy with toceranib phosphate and pamidronate was initiated. Toceranib was administered for 3 months without the development of any adverse effects except mild neutropenia. However, 3 months after initiating treatment, the toceranib was discontinued due to moderate gastrointestinal disturbances. Over the next 2 months, a left mandibular bone mass and cortical bone destruction in the bilateral tibia and tarsal joint were identified on CT. The patient became unwilling to eat and was noted to have severe skeletal pain. The anorexia and lethargy were progressively worsening and the owner decided to euthanize the patient. A necropsy was performed and the patient was definitively diagnosed with disseminated histiocytic sarcoma based on histopathologic and immunohistochemical analyses. This report describes a Miniature Schnauzer dog with DHS managed with surgical removal and metronomic chemotherapy with toceranib that survived with an improved quality of life for 7 months.

• BMB Reports
• /
• v.54 no.9
• /
• pp.470-475
• /
• 2021

Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

• Journal of Veterinary Clinics
• /
• v.28 no.3
• /
• pp.310-313
• /
• 2011

A 6-year-old female Shih-tzu dog was referred with left elbow joint mass associated with weight bearing lameness. Ultrasonography demonstrated an encapsulated hyperechoic mass at the left elbow joint. Radiography was performed on elbow joint, chest, and abdomen, but there was no evidence of metastasis. Clinicopathologic examination revealed the existence of neoplastic cells with anisocytosis, pleomorphism and increased nuclear-cytoplasmic ratio. The left forelimb was amputated for cure. Histopathological examination diagnosed the mass as a malignant peripheral nerve sheath tumor. During the 4 weeks follow-up, the patient showed full remission and adopted to walk with remaining three legs. Thereafter, the tumor recurred after 5 months of first surgery at the operation site and other two cutaneuos regions. Cytology test revealed the mesenchymal originated tumor cells with malignancy. These tumors were surgically removed and histopathological examination of the resected tissue revealed the recurrence of primary tumor and metastasis. Metronomic therapy with cyclophophamide (10 mg/$m^2$, PO, sid) and piroxicam (0.3 mg/kg, PO, sid) had been adopted for 5 months. At 26 months of follow up after the first surgery, the dog alive with satisfactory quality of life. Aggressive surgical resection with metronomic chemotherapy should be the most effective treatment for malignant peripheral nerve sheath tumor.

• Korean Journal of Veterinary Research
• /
• v.63 no.4
• /
• pp.38.1-38.6
• /
• 2023

Canine T-zone lymphoma (TZL) is an indolent form of T-cell lymphoma. Conservative management is usually recommended; however, chemotherapy may be considered for symptomatic or progressive cases. Herein, we describe two dogs with generalized peripheral lymphadenopathy and peripheral blood lymphocytosis at presentation. One dog presented with gross lesions on the tongue. Flow cytometric immunophenotyping and cytological examinations demonstrated findings consistent with those of TZL. Chemotherapy with chlorambucil and prednisolone was administered, which resulted in improvement of the condition without any adverse events. Chemotherapy with chlorambucil may be considered as an appropriate choice for treating canine TZL.

• Journal of Korean Neurosurgical Society
• /
• v.58 no.5
• /
• pp.426-431
• /
• 2015

Objective : The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. Methods : Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at $50mg/m^2/day$ until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). Results : The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was $22.7{\pm}24.1/mm^2$ (mean${\pm}$standard deviation), and this was lower than that of the initial tumor ($61.4{\pm}32.7/mm^2$) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. Conclusion : The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.

• Korean Journal of Veterinary Service
• /
• v.46 no.3
• /
• pp.249-253
• /
• 2023

A 12-year-old neutered male Maltese was brought to our hospital with loss of appetite, generalized alopecia, anemia, and a palpable abdominal mass. Ultrasonography revealed multiple abdominal masses in the liver and spleen. Subsequently, splenectomy and liver biopsy were performed, and the masses were histologically diagnosed as metastatic fibrosarcomas of unknown primary origin. The owner refused further investigations such as computed tomography and hepatectomy, therefore, we decided to initiate chemotherapy in the form of metronomic therapy with toceranib phosphate, which has several advantages, such as better tolerability, low cost, and convenience. The size and number of hepatic fibrosarcomas continued to increase despite continued administration of toceranib (10 mg/dog, PO, q48h). The dog died approximately 43 days after initiation of the toceranib treatment. To the best of our knowledge, this is the first report on toceranib therapy for metastatic hepatic fibrosarcoma in a dog.

• Current Optics and Photonics
• /
• v.3 no.1
• /
• pp.54-65
• /
• 2019

To develop a biomarker predicting tumor treatment efficacy is helpful to reduce time, medical expenditure, and efforts in oncology therapy. In clinics, microvessel density using immunohistochemistry has been proposed as an indicator that correlates with both tumor size and metastasis of cancer. In the preclinical study, we hypothesized that vascular morphometrics using optical coherence tomography angiography (OCTA) could be potential indicators to estimate the treatment efficacy of breast cancer. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber which was applied to a nude mouse, and the change in vascular morphology was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily OCTA maximum intensity projection map, multiple vessel parameters (vessel skeleton density, vessel diameter index, fractal dimension, and lacunarity) were compared with the tumor size in no tumor, treated tumor, and untreated tumor cases. Although each case has only one animal, we found that the vessel skeleton density (VSD), vessel diameter index and fractal dimension (FD) tended to be positively correlated with tumor size while lacunarity showed a partially negative correlation. Moreover, we observed that the changes in the VSD and FD are prior to the morphological change of the tumor. This feasibility study would be helpful in evaluating the tumor vascular response to treatment in preclinical settings.