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1.
Vet Radiol Ultrasound ; 64(6): 1099-1102, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37800663

RESUMEN

Most primary cardiac tumors in dogs are located in the right atrium/atrial appendage, with hemangiosarcoma being the most common. The aims of this retrospective, case series were to describe outcomes for seven dogs with right atrial tumors treated with hypofractionated intensity-modulated radiotherapy and concurrent vinblastine and propranolol. One dog had a complete response, four dogs had partial responses and two dogs had stable disease after treatment. Effusions resolved in all dogs. Median progression-free survival was 290 days. Five dogs died from metastatic disease, one dog from unrelated neoplasia, and one dog is alive. Median overall survival was 326 days. Three dogs with confirmed hemangiosarcoma survived 244, 326, and 445 days. Two dogs developed clinically significant, but nonfatal, cardiac arrhythmias. One dog that received three courses of radiation had subclinical myocardial and arterial fibrosis at necropsy. Hypofractionated chemoradiotherapy was well tolerated and may provide clinical benefit in dogs with right atrial tumors.


Asunto(s)
Apéndice Atrial , Enfermedades de los Perros , Hemangiosarcoma , Radioterapia de Intensidad Modulada , Perros , Animales , Radioterapia de Intensidad Modulada/veterinaria , Estudios Retrospectivos , Apéndice Atrial/patología , Hemangiosarcoma/terapia , Hemangiosarcoma/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/radioterapia
2.
Vet Radiol Ultrasound ; 64(5): 789-797, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37582508

RESUMEN

The toxicity criteria of the veterinary radiation therapy oncology group (VRTOG) version 2 guidelines are a substantial update to reflect significant advances in radiation oncology over the last three decades. Radiation therapy techniques provide precise and spatially accurate radiation delivery, which facilitates treating tumors in more anatomic locations and incorporating hypofractionated protocols. The purpose of this update is to aid radiation oncology teams in capturing and grading clinically relevant data that impacts the decision-making process in everyday practice and the assessment of clinical trials involving radiation therapy. A dedicated committee initially updated the criteria to include more anatomical sites and grades to characterize a broad spectrum of possible radiation-induced acute and late tissue changes. Through the revision process, which solicited and incorporated feedback from all radiation oncologists within the American College of Veterinary Radiology (ACVR) and specialists outside the ACVR, the authors endeavored to create a grading structure reflective of clinical decision-making in daily radiation oncology. The updated VRTOG v2 toxicity criteria guideline complements the updated Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) guidelines. Because radiation oncology continues to progress rapidly, the VRTOG toxicity criteria should be regularly updated as adverse event data that will be collected following this update further informs the practice of radiation oncology.


Asunto(s)
Oncología Médica , Oncología por Radiación , Animales
3.
Vet Radiol Ultrasound ; 61(6): 718-725, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32713101

RESUMEN

Dogs with sinonasal tumors with cribriform plate lysis (modified Adams' stage 4) treated with non-conformal definitive radiotherapy (RT) have short median survivals of 6-7 months. Intensity-modulated radiotherapy with its greater conformality and tumor dose homogeneity may result in more favorable outcomes. Dogs with epithelial or mesenchymal sinonasal tumors and CT evidence of cribriform lysis that received 10 daily fractions of 4.2 Gray using IMRT by helical tomotherapy were included in this single-institution retrospective case series study. Dogs with distant metastasis, previous treatment, or concurrent chemotherapy were excluded. Based on CT, tumors were divided into two groups: cribriform plate lysis only (stage 4a) or intracranial extension (stage 4b). Twenty-nine dogs were included, 23 with carcinoma and six with sarcoma. Eight dogs had stage 4b tumors; two presented with neurologic signs. Two dogs had lymph node metastasis at diagnosis, one confirmed and one suspected. Radiation dose distributions were standardized and patient positioning for RT was verified daily using on-board megavoltage CT. All evaluable dogs had improvement of clinical signs. Median progression free survival was 177 days (95% CI, 128-294 days). Median overall survival was 319 days (95% CI, 188-499 days). Radiotherapy was well tolerated. The most common side effect was grade 1 or 2 oral mucositis. Two dogs that received additional treatment at progression (stereotactic RT [1]; surgery [1]) developed significant late effects. Image-guided definitive-intent IMRT may improve survival in dogs with modified Adams' stage 4 sinonasal tumors and is associated with low morbidity. Intracranial tumor extension was not prognostic in this cohort of uniformly treated dogs.


Asunto(s)
Enfermedades de los Perros/radioterapia , Neoplasias Nasales/veterinaria , Senos Paranasales , Sarcoma/veterinaria , Animales , Supervivencia sin Enfermedad , Enfermedades de los Perros/mortalidad , Perros , Femenino , Metástasis Linfática , Masculino , Neoplasias Nasales/patología , Neoplasias Nasales/radioterapia , Planificación de la Radioterapia Asistida por Computador/veterinaria , Radioterapia de Intensidad Modulada/veterinaria , Registros/veterinaria , Estudios Retrospectivos , Sarcoma/radioterapia , Sarcoma/secundario
4.
Vet Radiol Ultrasound ; 61(4): 471-480, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32323424

RESUMEN

Canine oral melanoma (OM) is an aggressive cancer with a high rate of metastasis. Surgery and/or radiotherapy (RT) are effective local treatments, yet many dogs succumb to distant metastasis. Immunotherapy represents an attractive strategy for this potentially immunogenic tumor. The objective of this multi-institutional retrospective study was to examine the clinical outcome of dogs with OM treated with ONCEPT melanoma vaccine. Most dogs also underwent surgery and/or RT (8 Gy × four weekly fractions). Dogs with distant metastasis at diagnosis and those receiving concurrent chemotherapy were excluded. One hundred thirty-one dogs treated with ONCEPT were included: 62 had adequate local tumor control defined as complete tumor excision or irradiation of residual microscopic disease; 15 were treated in the microscopic disease setting following an incomplete excision without adjuvant RT; and 54 had gross disease. Median time to progression, median progression-free survival, and median tumor-specific overall survival were 304, 260, and 510 days, respectively. In multivariable analysis, presence of gross disease correlated negatively with all measures of clinical outcome. Other negative prognostic indicators were primary tumor ≥2 cm, higher clinical stage (stages 2 and 3), presence of lymph node metastasis at diagnosis, and caudal location in the oral cavity. Radiotherapy had a protective effect against tumor progression. To date, this is the largest reported series of dogs with OM treated with ONCEPT. Several previously reported prognostic indicators were confirmed.


Asunto(s)
Vacunas contra el Cáncer/uso terapéutico , Terapia Combinada/veterinaria , Enfermedades de los Perros/terapia , Melanoma/veterinaria , Neoplasias de la Boca/veterinaria , Radioterapia Adyuvante/veterinaria , Animales , Terapia Combinada/métodos , Perros , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/diagnóstico por imagen , Neoplasias de la Boca/terapia , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
5.
Vet Radiol Ultrasound ; 61(4): 481-489, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32356907

RESUMEN

Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three-dimensional conformal radiotherapy, reports of definitive-intent, IMRT for canine intracranial tumors are lacking. Intensity-modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi-institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty-two dogs treated with fractionated, definitive-intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45-50 Gy (2.25-2.5 Gy per fraction in 18-20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3-26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity-modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.


Asunto(s)
Neoplasias Encefálicas/veterinaria , Enfermedades de los Perros/radioterapia , Neoplasias Meníngeas/veterinaria , Radioterapia Conformacional/veterinaria , Radioterapia de Intensidad Modulada/veterinaria , Animales , Neoplasias Encefálicas/radioterapia , Perros , Femenino , Masculino , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Meningioma/veterinaria , Dosificación Radioterapéutica/veterinaria , Planificación de la Radioterapia Asistida por Computador/métodos , Planificación de la Radioterapia Asistida por Computador/veterinaria , Radioterapia Conformacional/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos
6.
Vet Radiol Ultrasound ; 60(1): 93-99, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30180282

RESUMEN

Radiotherapy is the treatment of choice for non-resectable canine thyroid carcinoma. High tumor response rates and median survival times of 2 years or longer have been previously reported with conventionally fractionated and hypofractionated protocols, even in dogs with distant metastasis. The objective of this retrospective, descriptive, case series study was to evaluate the clinical outcomes of dogs with thyroid carcinoma irradiated with palliative intent using hypofractionated radiotherapy at our institution. Medical records of 20 dogs treated between 1999 and 2014 were reviewed. All dogs had macroscopic primary tumors and presented with tumor-related clinical signs. Median longest tumor diameter was 10 cm. Nineteen dogs (95%) had metastasis (7/19 lymph node; 16/19 distant metastasis). Most dogs were treated with four weekly fractions of 6.5-8 Gy. Radiotherapy was well tolerated in 17 dogs; three died of respiratory compromise before completing radiotherapy. Eleven dogs received adjuvant chemotherapy. Five dogs experienced a local tumor response including two complete and three partial responses. Overall median survival time was 170 days (range, 1-824 days; 95% CI: 58-392 days). Of potential variables examined (radiation delivery system and protocol, tumor size and location, vascular/lymphatic invasion, metastatic disease, chemotherapy, tumor response), only achievement of complete or partial response was predictive of overall survival. In contrast to previously reported cohorts, dogs with clinical signs and stage IV disease predominated in this study. Previous studies may over-estimate survival following hypofractionated radiotherapy in dogs with advanced thyroid carcinoma.


Asunto(s)
Enfermedades de los Perros/radioterapia , Radioterapia/veterinaria , Neoplasias de la Tiroides/veterinaria , Animales , Perros , Femenino , Masculino , Radioterapia/métodos , Estudios Retrospectivos , Neoplasias de la Tiroides/radioterapia , Resultado del Tratamiento
7.
Vet Radiol Ultrasound ; 59(6): 786-795, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30062728

RESUMEN

Radiotherapy plays an important role in curative and palliative cancer treatment. As a novel radiation delivery technique, stereotactic radiotherapy utilizes three-dimensional-conformal treatment planning, high-precision beam delivery technology, and patient specific position verification to target tumors, often in one to five high-dose fractions. Currently, there is no consensus about best stereotactic radiotherapy practices in veterinary radiotherapy. The objective of this study was to document the breadth of perspectives, techniques, and applications of stereotactic radiotherapy in veterinary medicine. We conducted an online survey of American College of Veterinary Radiology members specializing in radiation oncology to assess how, when, and why stereotactic radiotherapy is being used. Both stereotactic radiotherapy users and nonusers completed the survey. The overall response and survey completion rates were 54% (67/123) and 87% (58/67), respectively. Overall, 55% of respondents reported providing stereotactic radiotherapy at their facility, with a median of 4.5 canine cases and one feline case per month. Delivery methods included C-arm linear accelerator with multi-leaf collimator, helical tomotherapy, and CyberKnife. Nonpituitary intracranial tumors, pituitary tumors, and sinonasal tumors were the most common cancers treated using stereotactic radiotherapy in both species. The most common fractionation scheme was three fractions of 10 Gy/fraction. The results of this survey suggest common availability of stereotactic radiotherapy in veterinary radiation facilities. These results provide valuable information regarding current stereotactic radiotherapy practices in veterinary medicine, and may provide an initial step toward standardizing methods and establishing consensus guidelines.


Asunto(s)
Radiocirugia/estadística & datos numéricos , Medicina Veterinaria/métodos , Animales , Gatos , Perros , Fraccionamiento de la Dosis de Radiación , Garantía de la Calidad de Atención de Salud/estadística & datos numéricos , Radiocirugia/instrumentación , Radiocirugia/métodos , Planificación de la Radioterapia Asistida por Computador/estadística & datos numéricos , Planificación de la Radioterapia Asistida por Computador/veterinaria , Estados Unidos , Medicina Veterinaria/instrumentación , Medicina Veterinaria/estadística & datos numéricos
8.
Vet Radiol Ultrasound ; 57(6): 639-645, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27465316

RESUMEN

Contouring variability is a significant barrier to the accurate delivery and reporting of radiation therapy. The aim of this descriptive study was to determine the variation in contouring radiation targets and organs at risk by participants within our institution. Further, we also aimed to determine if all individuals contoured the same normal tissues. Two canine nasal tumor datasets were selected and contoured by two ACVR-certified radiation oncologists and two radiation oncology residents from the same institution. Eight structures were consistently contoured including the right and left eye, the right and left lens, brain, the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Spinal cord, hard and soft palate, and bulla were contoured on 50% of datasets. Variation in contouring occurred in both targets and normal tissues at risk and was particularly significant for the GTV, CTV, and PTV. The mean metric score and dice similarity coefficient were below the threshold criteria in 37.5-50% and 12.5-50% of structures, respectively, quantitatively indicating contouring variation. This study refutes our hypothesis that minimal variation in target and normal tissue delineation occurs. The variation in contouring may contribute to different tumor response and toxicity for any given patient. Our results also highlight the difficulty associated with replication of published radiation protocols or treatments, as even with replete contouring description the outcome of treatment is still fundamentally influenced by the individual contouring the patient.


Asunto(s)
Enfermedades de los Perros/diagnóstico por imagen , Neoplasias Nasales/diagnóstico por imagen , Neoplasias Nasales/veterinaria , Radioterapia de Intensidad Modulada/veterinaria , Animales , Perros , Variaciones Dependientes del Observador
9.
Med Phys ; 51(6): 3924-3931, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626571

RESUMEN

Since 2010, there has been little published data on the state of equipment and infrastructure in veterinary radiation oncology clinical practice. These data are important not only to identify the status and use of technology within the veterinary radiation oncology community but also to help identify the extent of medical physics support. The purpose of our study is to report findings from a survey of veterinary radiation oncologists in the USA, Canada, and select centers outside of North America in 2022. A 40-question survey covering topics such as type of radiotherapy equipment, techniques offered, treatment planning systems and dose calculation algorithms, special techniques, board-certified radiation oncologists and residents, and extent of medical physics support was distributed through an online survey tool. Results from 40 veterinary radiation oncology institutions, with equipment explicitly used for veterinary care, suggest that the current state of practice is not dissimilar to what currently exists in human radiation oncology facilities; techniques and technologies commonly employed include flattening filter-free mode megavoltage beams, volumetric arc therapy, daily cone-beam computed tomography, image-guided radiation therapy, and sophisticated dose calculation algorithms. These findings suggest the need for modern radiation oncology acceptance testing, commissioning, and quality assurance programs within the veterinary community. The increase in veterinary radiation oncology residency positions and increasing sophistication of equipment suggests that increased levels of standardized medical physics support would benefit the veterinary radiation oncology community.


Asunto(s)
Oncología por Radiación , Encuestas y Cuestionarios , Animales , Humanos , Planificación de la Radioterapia Asistida por Computador , Medicina Veterinaria
10.
Vet Comp Oncol ; 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39367729

RESUMEN

Increasing numbers of dogs and cats with cancer are treated with stereotactic radiosurgery, stereotactic radiation therapy or stereotactic body radiotherapy (SRS, SRT or SBRT). We provide a systematic review of the current data landscape with a focus on technical and dosimetric data of stereotactic radiotherapy in veterinary oncology. Original peer-reviewed articles on dogs and cats with cancer treated with SRT were included. The systematic search included Medline via PubMed and EMBASE. The study was performed according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement. We assessed the manuscripts regarding outcome reporting, treatment planning, dose prescription, -delivery and -reporting as well as quality assurance. As of February 2024, there are 80 peer-reviewed publications on various disease entities on SRS, SRT and SBRT in veterinary medicine. Overall, we found often insufficient or highly variable technical data, with incomplete information to reproduce these treatments. While in some instances, technical factors may not impact clinical outcome, the variability found in protocols, outcome and toxicity assessments precludes accurate and reliable conclusions for a benefit of stereotactic radiotherapy for many of the treated diseases. In line with the extensive recommendations from human stereotactic radiotherapy practise, we propose a draft of reporting items for future stereotactic radiation treatments in veterinary medicine. SRS, SRT and SBRT have specific clinical and technological requirements that differ from those of standard radiation therapy. Therefore, a deep understanding of the methodologies, as well as the quality and precision of dose delivery, is essential for effective clinical knowledge transfer.

11.
Melanoma Res ; 34(4): 307-318, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-38768442

RESUMEN

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.


Asunto(s)
Enfermedades de los Perros , Interleucina-2 , Melanoma , Perros , Animales , Melanoma/radioterapia , Melanoma/inmunología , Melanoma/patología , Enfermedades de los Perros/radioterapia , Enfermedades de los Perros/inmunología , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Femenino , Masculino
12.
J Am Vet Med Assoc ; : 1-12, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39241800

RESUMEN

OBJECTIVE: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival. METHODS: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted. Selected variables were assessed for association with local progression and overall survival. RESULTS: 272 dogs were included. Histologic grade was reported in 249 dogs: 102 were grade 1 (40.9%), 120 were grade 2 (48.2%), and 27 were grade 3 (10.8%). Local progression was suspected or confirmed in 56 dogs. Local progression rates were similar for grade 1 (24 of 89 [26.7%]), grade 2 (23 of 111 [20.7%]), and grade 3 tumors (6 of 22 [27.3%]). Previous recurrence (P = .010) and subsequent distant metastasis (P = .014) were associated with more frequent local progression; intensity-modulated radiotherapy was associated with decreased local progression (P = .025) compared to other forms of delivery. Age (P = .049), grade (P = .009), previous recurrence (P = .009), and institution type for surgery (P = .043) were associated with overall survival. CONCLUSIONS: Outcomes for most dogs were good; however, the frequency of local progression indicates an ongoing need to critically appraise local management strategies, particularly for low-grade STS. Intensity-modulated radiotherapy was associated with lower rates of local progression and may be preferred to less precise forms of delivery. CLINICAL RELEVANCE: These data may guide clinicians when making decisions regarding dRT for management of STS.

13.
Plant Physiol ; 160(1): 556-68, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22829319

RESUMEN

AtPUB18 and AtPUB19 are homologous U-box E3 ubiquitin ligases in Arabidopsis (Arabidopsis thaliana). AtPUB19 is a negative regulator of abscisic acid (ABA)-mediated drought responses, whereas the role of AtPUB18 in drought responses is unknown. Here, loss-of-function and overexpression tests identified AtPUB18 as a negative regulator in ABA-mediated stomatal closure and water stress responses. The atpub18-2atpub19-3 double mutant line displayed more sensitivity to ABA and enhanced drought tolerance than each single mutant plant; therefore, AtPUB18 and AtPUB19 are agonistic. Stomatal closure of the atpub18-2atpub19-3 mutant was hypersensitive to hydrogen peroxide (H(2)O(2)) but not to calcium, suggesting that AtPUB18 and AtPUB19 exert negative effects on the ABA signaling pathway downstream of H(2)O(2) and upstream of calcium. AtPUB22 and AtPUB23 are other U-box E3 negative regulators of drought responses. Although atpub22atpub23 was more tolerant to drought stress relative to wild-type plants, its ABA-mediated stomatal movements were highly similar to those of wild-type plants. The atpub18-2atpub19-3atpub22atpub23 quadruple mutant exhibited enhanced tolerance to drought stress as compared with each atpub18-2atpub19-3 and atpub22atpub23 double mutant progeny; however, its stomatal behavior was almost identical to the atpub18-2atpub19-3 double mutant in the presence of ABA, H(2)O(2), and calcium. Overexpression of AtPUB18 and AtPUB19 in atpub22atpub23 effectively hindered ABA-dependent stomatal closure, but overexpression of AtPUB22 and AtPUB23 in atpub18-2atpub19-3 did not inhibit ABA-enhanced stomatal closure, highlighting their ABA-independent roles. Overall, these results suggest that AtPUB18 has a linked function with AtPUB19, but is independent from AtPUB22 and AtPUB23, in negative regulation of ABA-mediated drought stress responses.


Asunto(s)
Ácido Abscísico/farmacología , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Sequías , Estrés Fisiológico , Ubiquitina-Proteína Ligasas/metabolismo , Ácido Abscísico/metabolismo , Adaptación Fisiológica , Secuencia de Aminoácidos , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Calcio/metabolismo , Clorofila/análisis , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Prueba de Complementación Genética/métodos , Peróxido de Hidrógeno/farmacología , Manitol/farmacología , Datos de Secuencia Molecular , Fenotipo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/metabolismo , Raíces de Plantas/fisiología , Estomas de Plantas/metabolismo , Estomas de Plantas/fisiología , Plantas Modificadas Genéticamente/enzimología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Plantas Modificadas Genéticamente/fisiología , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética
14.
J Immunoassay Immunochem ; 34(3): 266-82, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23656247

RESUMEN

Optimizing cell culture conditions is important when studying cell proliferation and viability, particularly in response to cytotoxic compounds. Altered cell storage conditions can adversely impact proliferation and viability in mortal cell lines. However, little is known regarding the effects on immortal feline cell lines. In the present study, two feline injection-site sarcoma (ISS) cell lines were evaluated under standard culture conditions and three alternative storage/culture conditions for spontaneous proliferation rate and sensitivity to masitinib, a highly selective tyrosine kinase inhibitor with activity against primary and metastatic ISS cell lines. Cell viability was assessed by 7-aminoactinomycin D and cytology. Spontaneous proliferation did not significantly differ across the FBS concentrations (10% vs. 1%) for one cell line, however, with the other cell line spontaneous proliferation was significantly decreased in the 1% FBS 1-step technique, and the cold step technique at both 1% and 10% FBS. When normalized to untreated control cells, the IC50 values for masitinib were comparable across all culture techniques. Furthermore, apoptosis appeared to be the primary mechanism of this proliferation inhibition. Our preliminary findings suggest that select feline sarcoma cell lines cultured in 10% FBS yield comparable cytotoxicity data even when subjected to varying storage/culture conditions.


Asunto(s)
Técnicas de Cultivo de Célula/métodos , Preservación Biológica/métodos , Inhibidores de Proteínas Quinasas/farmacología , Sarcoma/metabolismo , Tiazoles/farmacología , Animales , Apoptosis/efectos de los fármacos , Benzamidas , Gatos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Piperidinas , Piridinas , Sarcoma/patología
15.
Vet Radiol Ultrasound ; 59(1): 10-12, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29134728
17.
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
18.
PLoS One ; 16(8): e0255798, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34383787

RESUMEN

RATIONALE: Murine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor in situ vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer. METHODS: The three component of the combination immuno-radiotherapy approach were employed either separately or in combination in companion dogs with advanced stage cancer. In situ vaccination was achieved through the administration of hypofractionated external beam radiotherapy and intratumoral hu14.18-IL2 fusion immunocytokine injections to the index tumor. In situ vaccination was subsequently combined with targeted radionuclide therapy using a theranostic pairing of IV 86Y-NM600 (for PET imaging and subject-specific dosimetry) and IV 90Y-NM600 (therapeutic radionuclide) prescribed to deliver an immunomodulatory 2 Gy dose to all metastatic sites in companion dogs with metastatic melanoma or osteosarcoma. In a subset of dogs, immunologic parameters preliminarily assessed. RESULTS: The components of the immuno-radiotherapy combination were well tolerated either alone or in combination, resulting in only transient low grade (1 or 2) adverse events with no dose-limiting events observed. In subject-specific dosimetry analyses, we observed 86Y-NM600 tumor:bone marrow absorbed-dose differential uptakes ≥2 in 4 of 5 dogs receiving the combination, which allowed subsequent safe delivery of at least 2 Gy 90Y-NM600 TRT to tumors. NanoString gene expression profiling and immunohistochemistry from pre- and post-treatment biopsy specimens provide evidence of tumor microenvironment immunomodulation by 90Y-NM600 TRT. CONCLUSIONS: The combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Interleucina-2/uso terapéutico , Melanoma/terapia , Osteosarcoma/terapia , Radiofármacos/uso terapéutico , Animales , Anticuerpos Monoclonales/efectos adversos , Médula Ósea/química , Médula Ósea/metabolismo , Médula Ósea/patología , Terapia Combinada , Perros , Estudios de Factibilidad , Femenino , Expresión Génica , Interleucina-2/efectos adversos , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/metabolismo , Linfocitos Infiltrantes de Tumor/citología , Linfocitos Infiltrantes de Tumor/metabolismo , Masculino , Melanoma/inmunología , Melanoma/patología , Melanoma/veterinaria , Osteosarcoma/inmunología , Osteosarcoma/veterinaria , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/efectos adversos , Radiofármacos/química , Vacunación , Radioisótopos de Itrio/química
19.
Vet Comp Oncol ; 18(4): 718-726, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32419347

RESUMEN

Thirty dogs with macroscopic plasma cell tumours (PCTs) were treated with radiation therapy (RT). Twelve patients were treated with palliative-intent prescriptions (range, 4-10 Gy/fraction (median, 7 Gy/fraction) for a total dose of 20 to 35 Gy (median total dose 30 Gy). Eighteen patients received definitive-intent prescriptions (range, 3.0-4.2 Gy/fraction (median, 3 Gy/fraction) for a total dose of 42 to 54 Gy (median total dose 48 Gy). Involved sites included the oral cavity, skin, multiple myeloma (MM)-associated lytic bone lesions, bone (solitary osseous plasmacytoma; SOP), nasal cavity, larynx, retrobulbar space, lymph node and rectum. Ninety-five percent of evaluable dogs had a complete (CR; 16/22) or partial response (PR; 5/22). Patients with MM experienced significant analgesia. The median progression-free survival (PFS) was 611 days (range: 36-2001 days). Events in the non-MM cases included in-field progression (5/26, 19%) and disseminated disease (5/26, 19%). The median survival time (MST) for all dogs was 697 days (range: 71-2075 days), and when only non-MM cases were considered, MST was 771 days (range: 71-2075 days). Fourteen patients were alive without disease progression or had died of unrelated causes. Achievement of a PR was associated with an inferior PFS and MST as compared with CR. Palliative-intent RT was associated with inferior MST as compared with definitive-intent RT. RT is a useful therapeutic modality for PCTs and tumour responses are often complete and durable, with protracted survivals. The optimal radiation dose and schedule are yet to be defined.


Asunto(s)
Enfermedades de los Perros/radioterapia , Plasmacitoma/veterinaria , Animales , Antineoplásicos/uso terapéutico , Terapia Combinada/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Enfermedades de los Perros/mortalidad , Perros , Femenino , Masculino , Plasmacitoma/tratamiento farmacológico , Plasmacitoma/mortalidad , Plasmacitoma/radioterapia , Supervivencia sin Progresión , Dosificación Radioterapéutica/veterinaria , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
20.
Vet Comp Oncol ; 18(4): 626-633, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32134553

RESUMEN

Treatment of epithelial sinonasal tumours in cats is not commonly reported. In the newer reports, palliative radiation protocols have been described more often than definitive-intent protocols. In this multi-institutional retrospective study, we included 27 cats treated with single-modality radiotherapy. Cats were irradiated using 10 daily fractions of 4.2 Gy. Three cats (11.1%) experienced a complete clinical response and 17 (63%) had a partial clinical response. Stable clinical disease was noted in three cats (11.1%). Four cats (14.8%) showed progression within 3 months following treatment. The median time to progression for all cases was 269 days (95 % confidence intervals [CI]: 225; 314). The proportion of cats free of progression at 1 and 2 years was 24% (95% CI: 22%; 26%) and 5% (95% CI: 5%; 6%), respectively. None of the prognostic factors evaluated were predictive of outcome (anaemia, tumour volume at the time of staging, modified Adams stage, intracranial involvement, facial deformity, epistaxis, inappetence or weight loss). Median overall survival (OS) for all deaths was 452 days (95% CI: 334; 571). The proportion of cats alive at 1 and 2 years was 57% (95% CI: 37%; 77%) and 27% (95% CI: 25%; 29%), respectively. Surprisingly, cats with epistaxis had a longer median OS of 828 days (95% CI: 356; 1301) compared to 296 days (95% CI: 85; 508) in cats without epistaxis, (P = .04, Breslow). Radiation therapy used as a single modality for the treatment of feline sinonasal carcinoma improved clinical signs and was well tolerated but progression within a year was common.


Asunto(s)
Carcinoma/veterinaria , Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/radioterapia , Neoplasias Glandulares y Epiteliales/veterinaria , Neoplasias de los Senos Paranasales/veterinaria , Animales , Carcinoma/mortalidad , Carcinoma/patología , Carcinoma/radioterapia , Gatos , Femenino , Masculino , Neoplasias Glandulares y Epiteliales/mortalidad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/radioterapia , Neoplasias de los Senos Paranasales/mortalidad , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/radioterapia , Portugal/epidemiología , Radioterapia/efectos adversos , Radioterapia/métodos , Radioterapia/veterinaria , Estudios Retrospectivos , Sobrevida
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