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1.
BMC Vet Res ; 20(1): 36, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297307

RESUMEN

BACKGROUND: Capecitabine is an oral prodrug of the active metabolite 5-fluorouracil, which has been used effectively in human colorectal, head and neck, and mammary carcinomas. Capecitabine has several properties that make it an attractive treatment option for dogs: (i) it is relatively inexpensive, (ii) it has a short half-life in humans, allowing for rapid plasma concentration changes to be achieved with dosage adjustments, (iii) it is effective for treating carcinomas in humans, for which there are no widely-effective oral chemotherapy options in dogs, and (iv) it is thought to preferentially target cancer cells due to different expression of thymidine phosphorylase, thereby decreasing the risk of off-target side effects. However, capecitabine has not been widely explored as a chemotherapy agent for dogs. The goal of this study was to determine the plasma disposition of capecitabine in dogs following a single oral dose and to document any adverse events associated with capecitabine administration over the course of 5 weeks. RESULTS: Capecitabine was well tolerated throughout the 5-week study period when administered to 5 dogs with naturally occurring carcinomas at 750 mg/m[Formula: see text] by mouth once daily for 14 consecutive days in a 3-week cycle. No dogs withdrew from the study due to adverse events or other causes. The median AUC[Formula: see text] was 890 h[Formula: see text]ng/ml (range 750-1100 h[Formula: see text]ng/ml); however, the maximum blood concentration and time to reach that concentration of capecitabine was highly variable after a single dose. CONCLUSIONS: Capecitabine appears well-tolerated as an oral chemotherapy agent for dogs with carcinomas, although individualized dosing may be necessary, and further studies are warranted.


Asunto(s)
Carcinoma , Enfermedades de los Perros , Perros , Humanos , Animales , Capecitabina/uso terapéutico , Proyectos Piloto , Desoxicitidina/efectos adversos , Fluorouracilo/efectos adversos , Carcinoma/tratamiento farmacológico , Carcinoma/veterinaria , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Administración Oral , Enfermedades de los Perros/etiología
2.
PLoS One ; 17(9): e0273705, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36099287

RESUMEN

Soft tissue sarcomas are pleiotropic tumors of mesenchymal cell origin. These tumors are rare in humans but common in veterinary practice, where they comprise up to 15% of canine skin and subcutaneous cancers. Because they present similar morphologies, primary sites, and growth characteristics, they are treated similarly, generally by surgical resection followed by radiation therapy. Previous studies have examined a variety of genetic changes as potential drivers of tumorigenesis and progression in soft tissue sarcomas as well as their use as markers for soft tissue sarcoma subtypes. However, few studies employing next generation sequencing approaches have been published. Here, we have examined gene expression patterns in canine soft tissue sarcomas using RNA-seq analysis of samples obtained from archived formalin-fixed and paraffin-embedded tumors. We provide a computational framework for using resulting data to categorize tumors, perform cross species comparisons and identify genetic changes associated with tumorigenesis. Functional overrepresentation analysis of differentially expressed genes further implicate both common and tumor-type specific transcription factors as potential mediators of tumorigenesis and aggression. Implications for tumor-type specific therapies are discussed. Our results illustrate the potential utility of this approach for the discovery of new therapeutic approaches to the management of canine soft tissue sarcomas and support the view that both common and tumor-type specific mechanisms drive the development of these tumors.


Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Animales , Carcinogénesis , Transformación Celular Neoplásica , Perros , Perfilación de la Expresión Génica , Humanos , Sarcoma/genética , Sarcoma/patología , Sarcoma/veterinaria , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/veterinaria , Transcriptoma
3.
Vet Comp Oncol ; 20(1): 293-303, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34655275

RESUMEN

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.


Asunto(s)
Antineoplásicos , Carcinoma , Enfermedades de los Perros , Neoplasias Nasales , Animales , Antineoplásicos/uso terapéutico , Carcinoma/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/radioterapia , Perros , Indoles , Neoplasias Nasales/tratamiento farmacológico , Neoplasias Nasales/radioterapia , Neoplasias Nasales/veterinaria , Estudios Prospectivos , Pirroles/uso terapéutico
4.
Clin Cancer Res ; 27(11): 3005-3016, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33753454

RESUMEN

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.


Asunto(s)
Neoplasias Óseas/terapia , Neoplasias Óseas/veterinaria , Enfermedades de los Perros/terapia , Osteosarcoma/terapia , Osteosarcoma/veterinaria , Mascotas , Sirolimus/administración & dosificación , Amputación Quirúrgica , Animales , Neoplasias Óseas/genética , Neoplasias Óseas/mortalidad , Carboplatino/administración & dosificación , Quimioterapia Adyuvante , Terapia Combinada/veterinaria , Enfermedades de los Perros/mortalidad , Perros , Osteosarcoma/genética , Osteosarcoma/mortalidad , Estudios Prospectivos , Transducción de Señal/efectos de los fármacos , Sirolimus/farmacología , Tasa de Supervivencia , Serina-Treonina Quinasas TOR/metabolismo , Resultado del Tratamiento
5.
J Vet Pharmacol Ther ; 43(2): 231-236, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31943234

RESUMEN

Prednisone resistance develops rapidly and essentially universally when dogs with lymphoma are treated with corticosteroids. We investigated naturally occurring mechanisms of prednisone resistance in seven dogs with naïve multicentric lymphoma, treated with oral prednisone; four dogs were administered concurrent cytotoxic chemotherapy. Expression of NR3C1α, ABCB1 (formerly MDR1), 11ß-HSD1, and 11ß-HSD2 mRNA was evaluated in neoplastic lymph nodes by real-time RT-PCR. Changes of expression levels at diagnosis and at time of clinical resistance to prednisone were compared longitudinally using a Wilcoxon signed-rank test. Clinical resistance to prednisone was observed after a median of 68 days (range: 7-348 days) after initiation of treatment. Relative to pretreatment samples, prednisone resistance was associated with decreased NR3C1α expression in biopsies of all dogs with high-grade lymphoma (six dogs, p=.031); one dog with indolent T-zone lymphoma had increased expression of NR3C1α. Resistance was not consistently associated with changes in ABCB1, 11ß-HSD1, or 11ß-HSD2 expression. Decreased expression of the glucocorticoid receptor (NR3C1α) may play a role in conferring resistance to prednisone in dogs with lymphoma. Results do not indicate a broad role for changes in expression of ABCB1, 11ß-HSD1, and 11ß-HSD2 in the emergence of prednisone resistance in lymphoma-bearing dogs.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Enfermedades de los Perros/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Linfoma/veterinaria , Prednisona/uso terapéutico , Receptores de Glucocorticoides/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Antineoplásicos Hormonales/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Estudios de Cohortes , Perros , Esquema de Medicación , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Linfoma/tratamiento farmacológico , Masculino , Prednisona/administración & dosificación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Glucocorticoides/genética
6.
Cancer Biother Radiopharm ; 35(1): 1-9, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31621382

RESUMEN

Purpose: Yttrium-90 (90Y)-polymer composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, the authors investigated the feasibility of treating feline and canine soft-tissue sarcomas as a model for nonresectable solid tumors in humans to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue. Materials and Methods: Five cats (Washington State University) and three dogs (University of Missouri) were selected for treatment from among veterinary clinic patients presenting with subcutaneous soft-tissue sarcomas. The therapeutic radiogel composite comprised two parts that were combined before therapy: (1) a calibrated activity of highly insoluble 90Y(YPO4) particles in a sterile, phosphate-buffered saline solution and (2) a resorbable hydrogel delivery vehicle containing a dissolved copolymer of poly-(DL-lactic acid-co-glycolic acid) and poly-(ethylene glycol). Sarcomas of anesthetized animals (five cats and three dogs) were injected with the 90Y-radiogel (10%-15% by tumor volume) using a parallel-needle grid pattern with ∼4-5-mm spacings with or without ultrasound guidance. After injection, the composite solution gelled within tumor interstitial spaces to solid phase upon reaching body temperatures to constrain the 90Y activity intratumorally. The animals were then imaged with computed tomography (CT) or positron emission tomography (PET)/CT and placed in radiation isolation for overnight monitoring and follow-up. Results: Gelation of the composite within tumor extracellular spaces confined the 90Y(YPO4) particles in place to deliver a planned radiation absorbed dose (100-320 Gy) to target tissue through complete decay. Response of the tumor tissue to 90Y-radiation therapy postexcision was evaluated by imaging, tumor resection, and histology. Correlation was observed on histopathology between tumor destruction and radiation dose. With uniform placement at high dose, the authors achieved complete remission or stable disease (at 1-2 months posttreatment). Conclusions: This study demonstrated successful injection of 90Y-polymer composite (radiogel) without discernable radiation dose to normal organs or other detrimental side effects. Animal patients recovered quickly from the injection procedure. The better therapeutic responses were observed at mean doses at or above 300 Gy.


Asunto(s)
Neoplasias/tratamiento farmacológico , Radioisótopos de Itrio/uso terapéutico , Animales , Gatos , Modelos Animales de Enfermedad , Perros , Humanos , Inyecciones , Dosificación Radioterapéutica , Radioisótopos de Itrio/farmacología
7.
Can Vet J ; 59(2): 136-142, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29386671

RESUMEN

The purpose of this study was to determine if metronomic administration of lomustine following palliative radiation therapy (RT) improved length of palliation and therefore survival in dogs with appendicular osteosarcoma compared to treatment with palliative radiation alone. A search of medical records identified dogs with appendicular osteosarcoma, treated with palliative RT (2 fractions of 8 Gray in a 24 hour time frame, day 0 and day 1; or day 0, 6 hours apart). Data collected included signalment, history, clinical signs, physical examination findings, clinicopathologic abnormalities, extent of disease, response, toxicity, other therapy, survival time, and whether dogs received metronomic lomustine (ML) or not. Of 86 patients, 43 received ML while 43 did not. Median survival time (MST) was not significantly different (P = 0.84), at 184 +/- 17 days for patients which received ML, and 154 +/- 20 days for those which did not. Metronomic lomustine administration was well-tolerated, but it did not improve survival in dogs with palliatively treated osteosarcoma.


Administration métronomique de lomustine après radiothérapie palliative pour le traitement des ostéosarcomes appendiculaires chez le chien. L'objectif de cette étude était de déterminer si l'administration métronomique de lomustine après radiothérapie palliative (RT) améliore la durée de palliation, et par conséquent la durée de vie, des chiens atteints d'ostéosarcome appendiculaire, en comparaison avec la radiothérapie seule. Les dossiers médicaux des chiens atteints d'ostéosarcome appendiculaire traités par radiothérapie palliative (2 fractions de 8 Gray dans un intervalle de 24 heures, jour 0 et jour 1; ou jour 0, à 6 heures d'intervalle) ont été identifiés et évalués. Les données collectées incluaient l'anamnèse, les commémoratifs, les anomalies de l'examen clinique et des analyses de laboratoires, les résultats du bilan d'extension, la réponse au(x) traitement(s), le développement de toxicités, d'éventuelles autres thérapies prodiguées, la durée de vie et si les chiens avaient été traités avec de la lomustine ou non. Sur 86 patients, 43 ont reçu de la lomustine tandis que 43 n'en ont pas reçu. La médiane de survie (MST) n'était pas significativement différente (P = 0.84), 184 +/− 17 jours pour les patients traités avec de la lomustine, et 154 +/− 20 jours pour ceux n'ayant pas reçu de lomustine. L'administration métronomique de lomustine était bien tolérée mais ne prodigua pas d'amélioration de la durée de vie lors de la prise en charge palliative des chiens atteints d'ostéosarcome.(Traduit par les auteurs).


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Lomustina/uso terapéutico , Osteosarcoma/veterinaria , Radioterapia/veterinaria , Animales , Antineoplásicos/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/radioterapia , Perros , Extremidades , Femenino , Lomustina/administración & dosificación , Masculino , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/radioterapia , Cuidados Paliativos , Estudios Retrospectivos
8.
Int J Toxicol ; 36(2): 104-112, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28403743

RESUMEN

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.


Asunto(s)
Colorantes Fluorescentes , Verde de Indocianina/análogos & derivados , Venenos de Escorpión , Animales , Proteínas del Sistema Complemento/análisis , Perros , Hipersensibilidad a las Drogas/sangre , Femenino , Colorantes Fluorescentes/farmacocinética , Colorantes Fluorescentes/toxicidad , Células HEK293 , Histamina/sangre , Humanos , Verde de Indocianina/farmacocinética , Verde de Indocianina/toxicidad , Macaca fascicularis , Masculino , Ratones , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Ratas Sprague-Dawley , Venenos de Escorpión/sangre , Venenos de Escorpión/farmacocinética , Venenos de Escorpión/toxicidad
9.
Vet Radiol Ultrasound ; 57(3): 341-51, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26841125

RESUMEN

Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross-sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once-daily fractions (Monday-Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first-line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction.


Asunto(s)
Carcinoma de Células Transicionales/veterinaria , Enfermedades de los Perros/radioterapia , Neoplasias Urogenitales/veterinaria , Animales , Carcinoma de Células Transicionales/radioterapia , Perros , Cuidados Paliativos , Sobrevida , Uretra/patología , Vejiga Urinaria/patología , Neoplasias Urogenitales/radioterapia
10.
Cancer Res ; 75(20): 4283-91, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26471914

RESUMEN

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.


Asunto(s)
Medios de Contraste , Diagnóstico por Imagen/métodos , Colorantes Fluorescentes , Neoplasias/diagnóstico , Adolescente , Animales , Niño , Preescolar , Medios de Contraste/administración & dosificación , Diagnóstico por Imagen/instrumentación , Modelos Animales de Enfermedad , Perros , Femenino , Colorantes Fluorescentes/administración & dosificación , Humanos , Verde de Indocianina/administración & dosificación , Verde de Indocianina/análogos & derivados , Cuidados Intraoperatorios , Masculino , Neoplasias/patología , Reproducibilidad de los Resultados , Venenos de Escorpión/administración & dosificación
11.
Am J Vet Res ; 74(2): 257-61, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23363351

RESUMEN

OBJECTIVE: To determine whether Border Collies (ATP binding cassette subfamily B1 gene [ABCB1] wildtype) were more likely than other breeds to develop vincristine-associated myelosuppression (VAM) and, if so, whether this was caused by a mutation in ABCB1 distinct from ABCB1-1Δ. ANIMALS: Phase 1 comprised 36 dogs with the ABCB1 wildtype, including 26 dogs with lymphoma (5 Border Collies and 21 dogs representing 13 other breeds) treated with vincristine in a previous study; phase 2 comprised 10 additional Border Collies, including 3 that developed VAM and 7 with an unknown phenotype. PROCEDURES: For phase 1, the prevalence of VAM in ABCB1-wildtype Border Collies was compared with that for ABCB1-wildtype dogs of other breeds with data from a previous study. For phase 2, additional Border Collies were included. Hematologic adverse reactions were graded with Veterinary Co-operative Oncology Group criteria. Genomic DNA was used to amplify and sequence all 27 exons of the canine ABCB1. Sequences from affected dogs were compared with those of unaffected dogs and dogs of unknown phenotype. RESULTS: 3 of 5 Border Collies with the ABCB1 wildtype developed VAM; this was significantly higher than the proportion of other dogs that developed VAM (0/21). A causative mutation for VAM in Border Collies was not identified, although 8 single nucleotide polymorphisms in ABCB1 were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Breed-associated sensitivity to vincristine unrelated to ABCB1 was detected in Border Collies. Veterinarians should be aware of this breed predisposition to VAM. Causes for this apparent breed-associated sensitivity should be explored.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Antineoplásicos Fitogénicos/efectos adversos , Enfermedades de los Perros/genética , Predisposición Genética a la Enfermedad , Linfoma/veterinaria , Polimorfismo de Nucleótido Simple , Vincristina/efectos adversos , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Enfermedades de los Perros/sangre , Perros , Linfoma/sangre , Linfoma/genética , Reacción en Cadena de la Polimerasa/veterinaria , Especificidad de la Especie
12.
Vet Radiol Ultrasound ; 52(5): 548-54, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21689203

RESUMEN

Cytologic sampling of the ultrasonographically normal spleen and liver is not implemented routinely in the clinical staging of canine cutaneous mast cell tumors and normal ultrasound findings are often accepted as sufficient evidence for ruling out splenic or liver metastasis. Our objective was to define the specificity and sensitivity of ultrasound findings for diagnosis of mast cell infiltration when verified with cytologic evaluation, and to define the prognostic role of cytologic evaluation of liver and splenic aspirates. Dogs with a diagnosis of clinically aggressive grade II, or grade III mast cell tumor treated with a combination vinblastine/CCNU chemotherapy protocol, were selected retrospectively based on availability of cytologic evaluation of spleen plus or minus liver for staging. Out of 19 dogs, 10 dogs had a grade II tumor and nine a grade III tumor. Seven dogs had mast cell infiltration of the spleen, liver, or both. The sensitivity of ultrasound for detecting mast cell infiltration was 43% for the spleen and 0% for the liver. Dogs with positive cytologic evidence of mast cell infiltration to spleen, liver, or both had significantly shorter survival (100 vs. 291 days) than dogs without evidence of mast cell infiltration (P<0.0001). Routine splenic aspiration should be performed regardless of ultrasonographic appearance in dogs with a clinically aggressive mast cell tumor.


Asunto(s)
Enfermedades de los Perros/diagnóstico por imagen , Sarcoma de Mastocitos/secundario , Sarcoma de Mastocitos/veterinaria , Neoplasias Cutáneas/veterinaria , Animales , Citodiagnóstico/veterinaria , Enfermedades de los Perros/diagnóstico , Perros , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/veterinaria , Sarcoma de Mastocitos/diagnóstico por imagen , Pronóstico , Neoplasias Cutáneas/patología , Bazo/diagnóstico por imagen , Bazo/patología , Neoplasias del Bazo/diagnóstico por imagen , Neoplasias del Bazo/secundario , Neoplasias del Bazo/veterinaria , Ultrasonografía
13.
Compend Contin Educ Vet ; 32(4): E3, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20949417

RESUMEN

Although the diagnosis of cancer is relatively uncommon in horses, tumors do occur in this species. Surgery, radiation, and chemotherapy are traditional cancer treatments in all species. In equine patients, surgery has often been the only treatment offered; however, not all tumors can be controlled with surgery alone. In small animal oncology, newer and better therapies are in demand and available. Radiation therapy is often used to control or palliate tumors locally, especially to satisfy clients who demand sophisticated treatments. The large size of equine patients can make radiation therapy difficult, but it is a valuable tool for treating cancer and should not be overlooked when treating horses.


Asunto(s)
Enfermedades de los Caballos/radioterapia , Neoplasias/veterinaria , Animales , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Enfermedades de los Caballos/cirugía , Caballos , Neoplasias/radioterapia , Neoplasias/cirugía
14.
Vet Radiol Ultrasound ; 50(3): 314-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19507399

RESUMEN

Thirty dogs with spontaneous tumors were irradiated with proton therapy using a novel spot scanning technique to evaluate the safety and efficacy of the system, and to study the acute and late radiation reactions. Nasal tumors, soft tissue sarcomas, and miscellaneous tumors of the head were treated with a median total dose of 52.5 Gy given in 3.5 Gy fractions. Acute effects, late effects, tumor response, and outcome were analyzed. No unexpected radiation reactions were seen, however two dogs did develop in-field osteosarcoma, and one dog developed in-field bone necrosis. Complete response to therapy was seen in 40% (12/30), partial response in 47% (14/30), and no response in 13% (4/30). Median survival for all dogs was 385 days (range of 14-4583 days). Dogs with nasal cavity tumors had a median survival of 385 days (range of 131-1851 days) and dogs with soft tissue sarcomas had a median survival time of 612 days (range of 65-4588 days). Treatment outcome was similar to historical controls. This new proton spot scanning technique proved to be safe and reliable.


Asunto(s)
Enfermedades de los Perros/radioterapia , Neoplasias/veterinaria , Animales , Perros , Neoplasias/radioterapia , Protones , Traumatismos por Radiación/veterinaria , Dosificación Radioterapéutica/veterinaria , Radioterapia Conformacional/veterinaria
15.
J Am Anim Hosp Assoc ; 45(1): 24-32, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19122061

RESUMEN

Fifty-eight dogs with lytic or proliferative bone lesions were treated with a radiation protocol of two 8-Gy fractions over 2 consecutive days. The protocol was well tolerated, with no increase in early or late effects over previously published protocols. Forty-three (91%) of 47 dogs responded positively to radiation, with a median time of 2 days to onset of pain relief. Median duration of pain relief was 67 days (range 12 to 503 days; mean 99+/-16 days). Median survival time for all dogs was 136 days (mean 179+/-18 days). Distal radial location was a positive prognostic indicator for survival (P=0.005).


Asunto(s)
Neoplasias Óseas/veterinaria , Enfermedades de los Perros/radioterapia , Osteosarcoma/veterinaria , Animales , Neoplasias Óseas/complicaciones , Neoplasias Óseas/radioterapia , Perros , Femenino , Estimación de Kaplan-Meier , Masculino , Osteosarcoma/complicaciones , Osteosarcoma/radioterapia , Dolor/etiología , Dolor/radioterapia , Dolor/veterinaria , Estudios Retrospectivos , Resultado del Tratamiento
16.
J Am Anim Hosp Assoc ; 44(4): 210-7, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18593858

RESUMEN

A 5-year-old, spayed female cat was referred because of a mass in the cranial mediastinum noted on thoracic radiographs. A thymoma was diagnosed following ultrasound and biopsy of the mass. Treatment was initiated with coarse-fraction radiation therapy using external-beam therapy (four fractions of 5 Gy). The mass responded, but granulocytopenia developed. Bone marrow examination showed a myeloid to erythroid ratio of approximately 1:1, with a left shift within the myeloid line. These findings, as well as the lack of toxic changes within the peripheral blood neutrophils, suggested immune-mediated destruction of peripheral granulocytes. Immune suppression with prednisone and cyclosporine was instituted. After 7 weeks, the neutrophil count returned to normal. The tumor was removed, and cyclosporine was reduced and eventually discontinued 3 weeks postsurgery.


Asunto(s)
Agranulocitosis/veterinaria , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/terapia , Timoma/veterinaria , Neoplasias del Timo/veterinaria , Agranulocitosis/complicaciones , Agranulocitosis/diagnóstico por imagen , Agranulocitosis/tratamiento farmacológico , Animales , Antiinflamatorios/administración & dosificación , Gatos , Ciclosporina/administración & dosificación , Femenino , Síndromes de Inmunodeficiencia/complicaciones , Síndromes de Inmunodeficiencia/veterinaria , Inmunosupresores/administración & dosificación , Neutropenia/etiología , Neutropenia/veterinaria , Prednisona/administración & dosificación , Traumatismos por Radiación/tratamiento farmacológico , Traumatismos por Radiación/veterinaria , Radiografía , Timoma/complicaciones , Timoma/diagnóstico , Timoma/terapia , Neoplasias del Timo/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/terapia , Resultado del Tratamiento , Washingtón
17.
Vet Radiol Ultrasound ; 48(5): 482-5, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17899987

RESUMEN

Nine cats with oral squamous cell carcinoma were treated with an accelerated radiation protocol (14 fractions of 3.5 Gy in 9 days). Radiation was administered twice daily with a 6hour break between treatments. Median overall survival was 86 +/- 110 days. Median survival for cats with a partial response (n=6) was 60 +/- 7 days, while median survival for cats with a complete response (n=3) was 298 +/- 187 days (P = 0.0639). The accelerated protocol was well tolerated and toxicity in the early and late period was manageable in all cats. Further modification of the protocol is warranted to extend survival.


Asunto(s)
Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Gatos/radioterapia , Neoplasias de la Boca/veterinaria , Animales , Carcinoma de Células Escamosas/radioterapia , Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/patología , Gatos , Femenino , Masculino , Neoplasias de la Boca/radioterapia , Dosis de Radiación , Radioterapia/veterinaria , Análisis de Supervivencia , Resultado del Tratamiento
18.
J Am Anim Hosp Assoc ; 43(2): 85-92, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17339285

RESUMEN

This retrospective study investigated a population of 96 dogs with newly diagnosed malignant lymphosarcoma that were treated with the commonly used University of Wisconsin-Madison (UW-M) chemotherapy protocol. Pretreatment characteristics were analyzed to determine prognostic factors. Dogs with higher World Health Organization (WHO) stages (including stage IV) and dogs with hypercalcemia were at significantly higher risk of relapse (P=0.018 and P=0.016, respectively). Dose reduction, treatment delays, and prior therapy with cortico-steroids were not associated with clinical outcome. First remission duration of 270 days was similar to historically reported data. Overall survival time of 218 days was much shorter than historical data.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Linfoma no Hodgkin/veterinaria , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades de los Perros/clasificación , Perros , Femenino , Estimación de Kaplan-Meier , Linfoma no Hodgkin/clasificación , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Factores de Tiempo
19.
J Am Anim Hosp Assoc ; 42(6): 472-6, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17088396

RESUMEN

A 10-year-old, female Newfoundland-cross dog was presented for evaluation of chronic intermittent unilateral epistaxis, nasal stertor, and sneezing. Nasal magnetic resonance imaging revealed a 3 x 5-cm mass in the left nasal cavity. Histopathological evaluation of nasal biopsies determined that the mass was a malignant melanoma. The mass was surgically resected and treated with bilateral opposed photon-beam radiation. This is the first report to describe the presentation, diagnosis, and treatment of an intranasal malignant melanoma in a dog.


Asunto(s)
Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/terapia , Melanoma/veterinaria , Cavidad Nasal , Neoplasias Nasales/veterinaria , Animales , Anticuerpos/análisis , Anticuerpos/metabolismo , Antígenos de Neoplasias/inmunología , Perros , Femenino , Inmunohistoquímica/veterinaria , Antígeno MART-1 , Imagen por Resonancia Magnética/veterinaria , Melanoma/diagnóstico , Melanoma/terapia , Proteínas de Neoplasias/inmunología , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/terapia , Radioterapia Adyuvante/veterinaria
20.
Vet Clin North Am Exot Anim Pract ; 9(3): 701-6, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16931393

RESUMEN

A 4-year-old, male, neutered ferret presented with squamous cell carcinoma of the right maxillary region associated with the tissues surrounding the upper canine tooth. A rostral maxillectomy was performed to excise the mass. Histopathologic examination showed questionable margins of tumor removal. Approximately 2 months after surgery, the ferret received a course of radiation therapy and is currently being monitored for tumor regrowth.


Asunto(s)
Carcinoma de Células Escamosas/veterinaria , Hurones , Neoplasias Maxilares/veterinaria , Animales , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Masculino , Neoplasias Maxilares/patología , Neoplasias Maxilares/radioterapia , Neoplasias Maxilares/cirugía , Recurrencia Local de Neoplasia/veterinaria , Resultado del Tratamiento
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