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1.
J Vet Intern Med ; 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517293

RESUMEN

BACKGROUND: Myeloma-related disorders (MRDs) are rare and poorly documented neoplasms of cats. HYPOTHESIS/OBJECTIVES: To describe clinical, clinicopathologic, and imaging findings, response to treatment, and survival time and to identify factors associated with shorter outcomes in cats with MRD. ANIMALS: Fifty cats with a diagnosis of MRD. METHODS: Cats with paraproteinemia confirmed by serum protein electrophoresis (SPE) and either intramedullary plasmacytosis >10%, marked cytonuclear atypia with intramedullary plasmacytosis that ranged between 5% and 10%, or cytologically or histologically confirmed visceral infiltration were retrospectively included from several veterinary referral centers. RESULTS: Bone marrow plasmacytosis and splenic or hepatic involvement were present in 17/27 cats (63%), 36/42 cats (86%), and 27/38 cats (71%), respectively. Anemia was reported in 33/49 cats (67%) and thrombocytopenia in 16/47 cats (34%). Some of the treatments that the cats received included melphalan and prednisolone (n = 19), cyclophosphamide and prednisolone (n = 10), chlorambucil and prednisolone (n = 4), prednisolone (n = 4), or other (n = 4). The overall response rates to melphalan, cyclophosphamide, and chlorambucil in combination with prednisolone were 87%, 90%, and 100%, respectively. Adverse events to melphalan or cyclophosphamide occurred in 65% and 23% of cats, respectively. Median survival time was 122 days (range, 0-1403) and was not significantly associated with chemotherapy protocol. Anemia (hazard ratio [HR], 3.1; 95% confidence interval [CI], 1.0-9.8) and thrombocytopenia (HR, 2.7; 95% CI, 1.2-6.0) were risk factors for shorter survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study confirmed the guarded prognosis of MRD in cats and identified risk factors for shorter survival times.

2.
Vet Comp Oncol ; 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38356238

RESUMEN

Specific data regarding outcome of cats with high-grade and large granular lymphocyte alimentary lymphoma (HGAL and LGL, respectively) treated with multi-agent chemotherapy are scarce. The aims of this multi-centric, retrospective study were to describe the outcome of cats with HGAL and LGL treated with COP- or CHOP-based chemotherapy and to identify potential prognostic factors. Cats with a cytological or histological diagnosis of HGAL or LGL lymphoma treated with COP- or CHOP-based protocol as first-line chemotherapy were included. Data regarding diagnosis, staging, treatment and follow-up were collected. Fifty-seven cats treated with CHOP (n = 37) or COP (n = 20) protocols were included. Complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were observed in 20%, 22%, 36% and 22% of cats, respectively, for an overall response rate of 42%. Median progression-free interval (PFI) was 148 days and overall median survival time (OST) was 131 days. Cats achieving CR, PR or SD showed significantly longer PFI (p < .01) and OST (p < .015) compared with cats with PD. Other positive prognostic factors in multi-variate analysis were rescue treatment (p < .001) and absence of lymph node involvement (p < .03). Negative prognostic factors were diffuse infiltration of the gastrointestinal tract (p = .035) and infiltration of a non-haematopoietic organ (p < .01).

3.
Can Vet J ; 64(10): 913-918, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37780482

RESUMEN

This article reports a case of a 10-year-old French bulldog initially seen for reluctance to move and episodes of pain. A magnetic resonance imaging study was undertaken in order to rule out a herniated disc. A large, retroperitoneal mass was visualized and cytological analysis suggested a neoplastic proliferation. The mass appeared to compress the caudal vena cava when viewed by abdominal CT scan. The mass was surgically removed. A nephrectomy was also carried out and aortic bleeding identified after dissection of adhesions. Despite these complications, the dog did well after the procedures. Postoperative checkups were normal. Histological and immunohistochemical analyses of the mass were compatible with a retroperitoneal paraganglioma. Key clinical message: This type of tumor is poorly described in the veterinary literature. As the behavior of this tumor type is not yet fully understood, each new description adds to our knowledge and should help in diagnosing and treating it more effectively in the future.


Paragangliome rétropéritonéal de découverte fortuite chez un bouledogue Français de 10 ans. Cet article expose le cas d'un chien mâle entier bouledogue Français de 10 ans présenté initialement pour des difficultés locomotrices et des manifestations algiques. Un examen d'imagerie par résonnance magnétique (IRM) est rapidement réalisé afin d'explorer l'hypothèse d'une hernie discale. Une volumineuse masse rétropéritonéale est alors mise en évidence. L'analyse cytologique de cette dernière est compatible avec un processus néoplasique. Après la réalisation d'un examen par tomodensitométrie de l'abdomen et la mise en évidence d'une compression marquée de la veine cave caudale par la masse, une prise en charge chirurgicale avec exérèse de la masse est décidée. Lors de l'intervention chirurgicale une néphrectomie est réalisée et un saignement aortique est identifié après la dissection des adhérences. Malgré ces complications, le chien se réveille bien et les contrôles post opératoires effectués sont satisfaisants. Les analyses histologiques et immunohistochimiques de la masse seront en faveur d'un paragangliome rétropéritonéal extra surrénalien.Message clinique clé :Ce type tumoral fait l'objet de peu de descriptions dans la littérature vétérinaire. Toute la lumière n'a pas encore été faite sur son comportement et chaque nouvelle description permet d'en enrichir les connaissances et donc de mieux comprendre ce type tumoral, ce qui, à l'avenir, pourra aider à le diagnostiquer plus facilement et à le traiter plus efficacement.(Traduit par les auteurs).


Asunto(s)
Enfermedades de los Perros , Paraganglioma , Neoplasias Retroperitoneales , Perros , Animales , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/cirugía , Neoplasias Retroperitoneales/veterinaria , Paraganglioma/diagnóstico por imagen , Paraganglioma/cirugía , Paraganglioma/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Imagen por Resonancia Magnética/veterinaria , Vena Cava Inferior , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía
4.
Front Oncol ; 12: 923679, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36419904

RESUMEN

Glioblastoma is considered the most common malignant primary tumor of central nervous system. In spite of the current standard and multimodal treatment, the prognosis of glioblastoma is poor. For this reason, new therapeutic approaches need to be developed to improve the survival time of the glioblastoma patient. In this study, we performed a preclinical experiment to evaluate therapeutic efficacy of 166Ho microparticle suspension administered by microbrachytherapy on a minipig glioblastoma model. Twelve minipigs were divided in 3 groups. Minipigs had injections into the tumor, containing microparticle suspensions of either 166Ho (group 1; n = 6) or 165Ho (group 2; n = 3) and control group (group 3; n = 3). The survival time from treatment to euthanasia was 66 days with a good state of health of all minipigs in group 1. The median survival time from treatment to tumor related death were 8.6 and 7.3 days in groups 2 and control, respectively. Statistically, the prolonged life of group 1 was significantly different from the two other groups (p < 0.01), and no significant difference was observed between group 2 and control (p=0.09). Our trial on the therapeutic effect of the 166Ho microparticle demonstrated an excellent efficacy in tumor control. The histological and immunohistochemical analysis showed that the efficacy was related to a severe 166Ho induced necrosis combined with an immune response due to the presence of the radioactive microparticles inside the tumors. The absence of reflux following the injections confirms the safety of the injection device.

5.
Vet Sci ; 9(9)2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-36136711

RESUMEN

Netrin-1 is a member of the laminin superfamily, and is known to interact with specific receptors, called dependence receptors. While upon netrin-1 binding these receptors initiate positive signaling, in absence of netrin-1, these receptors trigger apoptosis. Tumor cells can avoid apoptosis by inactivating these receptors or by gaining ligand expression. The aim of the present study was to investigate the expression of netrin-1, the ligand of dependence receptors, in canine healthy lymph nodes (LN), and in lymphomas and to evaluate efficiency of a netrin-1 interfering compound in cell cultures from canine lymphoma. Thirty-two control LN and 169 lymphomas were analyzed through immunohistochemistry. Netrin-1 was expressed in the nucleoli of lymphoid and non-lymphoid cells in controls. Acquisition of a cytoplasmic expression was present in B-cell lymphomas (23.1 % in low-grade and 50.6% in high-grade) and T-cell lymphomas (50.0 % in low-grade and 78.8 % in high-grade), with a significant difference between the high- and low-grade in B-cell lymphomas. Through flow cytometry, we showed a significant increase in netrin-1 expression in either high-grade B-cell and T-cell lymphomas (19 and 5, respectively) compared with healthy LN (5), likewise an RT-qPCR analysis demonstrated a significant increase in netrin-1 expression level in 14 samples of lymphomas compared with eight samples of healthy LN. A T-cell aggressive canine lymphoma cell line and four primary canine nodal lymphomas cell cultures were treated with a netrin-1 interfering antibody. Apoptosis by measuring caspase 3 activity was significantly increased in the cell line and viability was decreased in three of the four primary cell cultures. Together, these data suggest that netrin-1 expression is increased in lymphoma, and more specifically in high-grade lymphomas, and that netrin-1 can act as a survival factor for the neoplastic cells, and so be a therapeutic target.

6.
Vet Comp Oncol ; 20(4): 825-835, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35633310

RESUMEN

Mesothelioma is an uncommon cancer in dogs for which there is no established standard of care. Chemotherapy is often suggested despite no definitive proof of efficacy. The aim of this study was to evaluate the impact of chemotherapy on survival of dogs with mesothelioma. A retrospective multicentric study was carried out. To be included, dogs needed to present an evocative clinical evolution and a morphological diagnosis of mesothelioma. Exclusion of other cause of effusion and complete clinical follow-up were also required. Fourty dogs were included, 27 received chemotherapy (group 1) and 13 did not (group 2). Groups were heterogeneous regarding the proportion of animals undergoing surgery as part of their treatment (16 in group 1, 2 in group 2; p = .016) and homogeneous otherwise. Univariate analysis showed that dogs from group 1 survived significantly longer than dogs from group 2 (MST: 366 vs. 74 days; p < .001). Complete resolution of effusion after the first chemotherapy administration positively correlated with survival in group 1 (MST: 415 vs. 160 days; p < .01). All other variable tested had no significant impact on survival in univariate analysis, but dogs undergoing surgery and dogs having serous membranes' modification at medical imaging tended to survive longer. Multivariate analysis confirmed that chemotherapy was the sole variable independently associated with survival in our study (odds ratio 5.57-6.12; p < .01).


Asunto(s)
Enfermedades de los Perros , Mesotelioma , Perros , Animales , Estudios Retrospectivos , Enfermedades de los Perros/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Mesotelioma/veterinaria
7.
Vet Comp Oncol ; 20(2): 393-403, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34775666

RESUMEN

Overall prevalence of severe adverse events (sAE) has been poorly studied in veterinary medicine and peer-reviewed studies mostly focused on a single protocol, making it difficult to have a general overview. The aim of this retrospective study was to assess the frequency and risk factors of sAE secondary to various protocols of chemotherapy in dogs. Medical records of 155 dogs receiving chemotherapy between January 2013 and December 2018 were reviewed. Adverse events (AE) were graded according to Veterinary Comparative Oncology Group-common terminology criteria for AE (VCOG-CTCAE) grading system. Statistical analyses were performed to determine whether demographic, cancer type and chemotherapy protocol were associated with development of sAE and their consequences. AE were reported at least once in 124 (80%) dogs and sAE were observed in 50 (32.3%) dogs. Among them, 23 (14.8%) had gastro-intestinal and 31 (20.0%) had myelotoxic events. sAE led to hospitalisation in 37 (23.9%) dogs, to chemotherapy arrest in 12 (7.7%) dogs and to euthanasia or death in 9 (5.8%) dogs. Haematopoietic tumours were statistically associated with a higher frequency of sAE (p = .004), gastrointestinal sAE (p = .009) and hospitalisation (p = .004). A body weight over 10 kg was associated with less haematological sAE (p < .001). The use of a multi-agent protocol was highlighted as a risk factor for sAE (p = .038) and haematological sAE (p < .001). sAE following chemotherapy and leading to hospitalisation, chemo arrest or death were relatively common. A special attention during chemotherapy follow-up should be given to small dogs and those receiving multi-agent protocol or treated for haematopoietic tumours.


Asunto(s)
Enfermedades de los Perros , Neoplasias Hematológicas , Neoplasias , Animales , Protocolos de Quimioterapia Combinada Antineoplásica , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Perros , Neoplasias Hematológicas/tratamiento farmacológico , Neoplasias Hematológicas/veterinaria , Neoplasias/tratamiento farmacológico , Neoplasias/veterinaria , Estudios Retrospectivos
8.
Vet Clin Pathol ; 49(3): 476-483, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32955128

RESUMEN

Response to chemotherapy is one of the most important prognostic factors in dogs with lymphoma. The objective of this feasibility study was to evaluate if clinical responses to a specific cytotoxic agent (L-asparaginase) could be anticipated by measuring analyte concentrations in plasma and urine concentrations of lymphoma-bearing dogs. We hypothesized that potassium and phosphate concentrations in plasma and urine would be higher in dogs that completely responded to therapy. Plasma and urine samples of dogs with lymphoma were obtained before 12 and 24 hours after intramuscular L-asparaginase injections. Peripheral lymph node volumes were evaluated according to the Veterinary Cooperative Oncology Group standardized criteria. Plasma and urine electrolyte, calcium, phosphate, creatinine, urea, total protein, and albumin concentrations were measured, and the fractional excretions of each electrolyte were calculated. Statistical analyses compared complete vs partial responders using a linear regression model. Contrast analyses were also performed to differentiate the mean of each group, with adjustments made with the Benjamini-Hochberg procedure. Fourteen dogs were included, eight with complete responses, and six with partial responses. Plasma phosphate concentrations were significantly higher at 12 hours (P = .0003) and 24 hours (P = .009) after complete responses to therapy. This study demonstrates the potential use of plasma and urine analyte monitoring after chemotherapy induction. Plasma phosphate measurements represent a potential indicator of early responses to L-asparaginase therapy. Larger population studies are warranted to confirm these preliminary results.


Asunto(s)
Antineoplásicos , Enfermedades de los Perros , Linfoma no Hodgkin , Linfoma , Animales , Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Perros , Linfoma/tratamiento farmacológico , Linfoma/veterinaria , Linfoma no Hodgkin/veterinaria
9.
PLoS One ; 15(6): e0234772, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32555746

RESUMEN

Glioblastoma is the most aggressive primary brain tumor leading to death in most of patients. It comprises almost 50-55% of all gliomas with an incidence rate of 2-3 per 100,000. Despite its rarity, overall mortality of glioblastoma is comparable to the most frequent tumors. The current standard treatment combines surgical resection, radiotherapy and chemotherapy with temozolomide. In spite of this aggressive multimodality protocol, prognosis of glioblastoma is poor and the median survival remains about 12-14.5 months. In this regard, new therapeutic approaches should be developed to improve the life quality and survival time of the patient after the initial diagnosis. Before switching to clinical trials in humans, all innovative therapeutic methods must be studied first on a relevant animal model in preclinical settings. In this regard, we validated the feasibility of intratumoral delivery of a holmium (Ho) microparticle suspension to an induced U87 glioblastoma model. Among the different radioactive beta emitters, 166Ho emits high-energy ß(-) radiation and low-energy γ radiation. ß(-) radiation is an effective means for tumor destruction and γ rays are well suited for imaging (SPECT) and consequent dosimetry. In addition, the paramagnetic Ho nucleus is a good asset to perform MRI imaging. In this study, five minipigs, implanted with our glioblastoma model were used to test the injectability of 165Ho (stable) using a bespoke injector and needle. The suspension was produced in the form of Ho microparticles and injected inside the tumor by a technique known as microbrachytherapy using a stereotactic system. At the end of this trial, it was found that the 165Ho suspension can be injected successfully inside the tumor with absence or minimal traces of Ho reflux after the injections. This injection technique and the use of the 165Ho suspension needs to be further assessed with radioactive 166Ho in future studies.


Asunto(s)
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Holmio/química , Radiofármacos/administración & dosificación , Siloxanos/química , Animales , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Humanos , Masculino , Radiofármacos/química , Radiofármacos/metabolismo , Porcinos , Porcinos Enanos , Tomografía Computarizada de Emisión de Fotón Único , Trasplante Heterólogo
10.
BMC Vet Res ; 14(1): 232, 2018 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-30081964

RESUMEN

BACKGROUND: Canine breeds may be considered good animal models for the study of genetic predisposition to cancer, as they represent genetic clusters. From epidemiologic and case collection studies it emerges that some breeds are more likely to develop lymphoma or specific subtypes of lymphoma but available data are variable and geographically inconsistent. This study was born in the context of the European Canine Lymphoma Network with the aim of investigating the breed prevalence of canine lymphoma in different European countries and of investigating possible breed risk of lymphoma overall and/or different lymphoma subtypes. RESULTS: A total of 1529 canine nodal lymphoma cases and 55,529 control cases from 8 European countries/institutions were retrospectively collected. Odds ratios for lymphoma varied among different countries but Doberman, Rottweiler, boxer and Bernese mountain dogs showed a significant predisposition to lymphoma. In particular, boxers tended to develop T-cell lymphomas (either high- or low-grade) while Rottweilers had a high prevalence of B-cell lymphomas. Labradors were not predisposed to lymphoma overall but tended to develop mainly high-grade T-cell lymphomas. In contrast with previous studies outside of Europe, the European golden retriever population did not show any possible predisposition to lymphoma overall or to specific subtypes such as T-zone lymphoma. CONCLUSION: Further prospective studies with more precise and consistent subtype identification are needed to confirm our retrospective results and to create the basis for the investigation of possible genes involved in different predispositions.


Asunto(s)
Enfermedades de los Perros/etiología , Linfoma/veterinaria , Animales , Enfermedades de los Perros/epidemiología , Perros , Europa (Continente)/epidemiología , Linfoma/epidemiología , Linfoma/etiología , Linfoma de Células T/epidemiología , Linfoma de Células T/etiología , Linfoma de Células T/veterinaria , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Especificidad de la Especie
11.
J Neurosci Methods ; 282: 61-68, 2017 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-28284687

RESUMEN

BACKGROUND: Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. NEW METHOD: A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. RESULTS: Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. COMPARISON WITH EXISTING METHOD: Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic METHODS: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. CONCLUSION: This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Trasplante de Neoplasias , Porcinos Enanos , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Ciclosporina/sangre , Ciclosporina/farmacología , Femenino , Glioblastoma/diagnóstico por imagen , Glioblastoma/patología , Humanos , Inmunosupresores/sangre , Inmunosupresores/farmacología , Masculino , Porcinos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Carga Tumoral
12.
J Feline Med Surg ; 19(4): 351-357, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26767979

RESUMEN

Objectives The aim of the study was to describe the clinical outcome of 30 cats with non-ocular melanomas and to evaluate the association between clinical or pathological parameters and overall survival time. Methods The database of the animal histopathological laboratory of the National Veterinary School of Nantes (Oniris, Nantes, France) was retrospectively searched to identify cases of feline non-ocular melanomas between December 2009 and April 2014. For each case, clinical data, including signalment, location of the primary tumour, staging, treatment and outcome, were collected from the medical records or via interviews with referring veterinarians. Histological and immunohistochemical evaluation included mitotic index, cytonuclear atypias, junctional activity, Melan A and S100 immunostaining, and surgical margins. Univariate analysis to test the prognostic value of the different variables was performed by the Kaplan-Meier product limit method using the log-rank test of significance. Results Thirty cats were included in the study. Eleven had a cutaneous non-auricular melanoma, six had a tumour located on the pinna and 13 had a tumour in the oral cavity. Cats with auricular melanomas were significantly younger than cats with tumours in other locations. Location and presence of clinical signs were not of prognostic significance, but the achromic phenotype was significantly associated with a poorer prognosis. Twenty cats were treated with surgery and survived significantly longer than cats that received only medical treatment or that did not receive any treatment. According to our data, mitotic index, cytonuclear atypias, junctional activity, Melan A or S100 expression, and surgical margins were not associated with survival. Conclusions and relevance We show for the first time, in a large series, that the auricular form of melanoma affected significantly younger cats than other extraocular forms. Most feline non-ocular melanomas are malignant and achromic tumours are associated with a poorer prognosis. According to this study, surgery should be considered as a priority.


Asunto(s)
Enfermedades de los Gatos/epidemiología , Melanoma/veterinaria , Neoplasias Cutáneas/veterinaria , Animales , Enfermedades de los Gatos/etiología , Enfermedades de los Gatos/mortalidad , Enfermedades de los Gatos/cirugía , Gatos , Oído Externo , Femenino , Francia/epidemiología , Estimación de Kaplan-Meier , Masculino , Melanoma/epidemiología , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/epidemiología , Análisis de Supervivencia
13.
Eur J Pharm Biopharm ; 100: 85-93, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26777342

RESUMEN

Near-infrared (NIR) fluorescence imaging using FDA-approved indocyanine green (ICG) has been the subject of numerous studies during the past few years. It could constitute a potentially exciting new paradigm shift in veterinary oncology, especially to develop in vivo fluorescence imaging diagnostics and surgery guidance methods. The objective of this study was to evaluate the pharmacologic and toxicological characteristics in healthy beagle dogs of LipImage™ 815, a formulation made of NIR-dye-loaded lipid nanoparticles. The initial dosage for the evaluation of biodistribution was extrapolated from data in mice and then adapted to define the more adapted dose (MAD) according to the fluorescence results obtained in 5 dogs using a Fluobeam® 800 imaging device (phase 0 study). A single dose acute toxicity study was then performed (3 dogs, phase I study). Before the systemic administration of LipImage™ 815, the dogs presented a very mild residual fluorescence, particularly in the liver and kidneys. After injection, the plasma fluorescence continuously decreased, and the signal was relatively homogeneously distributed throughout the different organs, though more pronounced in the liver and to a lesser extent in the steroid-rich organs (adrenal, ovaries), intestines, lymph nodes and kidneys. A MAD of 2.0µg/kg was found. No evidence of acute or delayed general, hepatic, renal or hematologic toxicity was observed at 1-fold, 5-fold or 10-fold MAD. The results of this phase-0/phase-I study showed that an optimal dosage of LipImage™ 815 of 2.0µg/kg allowed the achievement of a fluorescence signal suitable for surgery guidance application without any acute side effects.


Asunto(s)
Colorantes Fluorescentes/química , Verde de Indocianina/química , Lípidos/química , Nanopartículas/química , Espectroscopía Infrarroja Corta , Animales , Perros , Femenino , Colorantes Fluorescentes/farmacocinética , Verde de Indocianina/farmacocinética , Indoles/química , Indoles/farmacocinética , Lípidos/farmacocinética , Masculino , Espectroscopía Infrarroja Corta/métodos , Distribución Tisular/efectos de los fármacos , Distribución Tisular/fisiología
14.
Transl Res ; 170: 73-88, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26746803

RESUMEN

The objective was to prospectively evaluate the application of intraoperative fluorescence imaging (IOFI) in the surgical excision of malignant masses in dogs, using a novel lipid nanoparticle contrast agent. Dogs presenting with spontaneous soft-tissue sarcoma or subcutaneous tumors were prospectively enrolled. Clinical staging and whole-body computed tomography (CT) were performed. All the dogs received an intravenous injection of dye-loaded lipid nanoparticles, LipImage 815. Wide or radical resection was realized after CT examination. Real-time IOFI was performed before skin incision and after tumor excision. In cases of radical resection, the lymph nodes (LNs) were imaged. The margin/healthy tissues fluorescence ratio or LN/healthy tissues fluorescence ratio was measured and compared with the histologic margins or LN status. Nine dogs were included. Limb amputation was performed in 3 dogs, and wide resection in 6. No adverse effect was noted. Fluorescence was observed in all 9 of the tumors. The margins were clean in 5 of 6 dogs after wide surgical resection, and the margin/healthy tissues fluorescence ratio was close to 1.0 in all these dogs. Infiltrated margins were observed in 1 case, with a margin/healthy tissues fluorescence ratio of 3.2. Metastasis was confirmed in 2 of 3 LNs, associated with LN/healthy tissues fluorescence ratios of 2.1 and 4.2, whereas nonmetastatic LN was associated with a ratio of 1.0. LipImage 815 used as a contrast agent during IOFI seemed to allow for good discrimination between tumoral and healthy tissues. Future studies are scheduled to evaluate the sensitivity and specificity of IOFI using LipImage 815 as a tracer.


Asunto(s)
Enfermedades de los Perros/cirugía , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias de los Tejidos Blandos/veterinaria , Cirugía Asistida por Computador/métodos , Animales , Medios de Contraste/administración & dosificación , Perros , Femenino , Fluorescencia , Colorantes Fluorescentes/administración & dosificación , Indoles/administración & dosificación , Cuidados Intraoperatorios/métodos , Metástasis Linfática/patología , Masculino , Nanopartículas/administración & dosificación , Estudios Prospectivos , Sarcoma/patología , Sarcoma/cirugía , Sarcoma/veterinaria , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/cirugía , Espectroscopía Infrarroja Corta/métodos , Tomografía Computarizada por Rayos X
15.
Immunobiology ; 221(1): 12-22, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26345430

RESUMEN

Dogs with lymphoma are established as good model for human non-Hodgkin lymphoma studies. Canine cell lines derived from lymphomas may be valuable tools for testing new therapeutic drugs. In this context, we established a canine T-cell line, PER-VAS, from a primary aggressive T-cell lymphoma with large granular morphology. Flow cytometric analysis revealed a stable immunophenotype: PER-VAS cells were positively labelled for CD5, CD45, MHC II and TLR3, and were negative for CD3, CD4 and CD8 expression. Although unstable along the culture process, IL-17 and MMP12 proteins were detectable as late as at passages 280 and 325i.e. respectively 24 and 29 months post isolation. At passage 325, PER-VAS cells maintained the expression of IL-17, CD3, CD56, IFNγ and TNFα mRNAs as shown by RT-PCR analysis. Stable rearrangement of the TCRγ gene has been evidenced by PCR. PER-VAS cells have a high proliferation index with a doubling time of 16.5h and were tumorigenic in Nude mice. Compared to the canine cell lines already reported, PER-VAS cells display an original expression pattern, close to NKT cells, which makes them valuable tools for in vitro comparative research on lymphomas.


Asunto(s)
Línea Celular/inmunología , Expresión Génica/inmunología , Linfoma de Células T/inmunología , ARN Mensajero/inmunología , Linfocitos T/inmunología , Animales , Antígenos CD/genética , Antígenos CD/inmunología , Línea Celular/patología , Perros , Efecto Fundador , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Inmunofenotipificación , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-17/genética , Interleucina-17/inmunología , Linfoma de Células T/genética , Linfoma de Células T/patología , Masculino , Ratones , Ratones Desnudos , ARN Mensajero/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Linfocitos T/patología , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/inmunología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología
16.
Can Vet J ; 56(2): 185-92, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25694669

RESUMEN

There are no evidence-based guidelines as to whether computed tomography (CT) or endoscopy should be selected as the first-line procedure when a nasal tumor is suspected in a dog or a cat and only one examination can be performed. Computed tomography and rhinoscopic features of 17 dogs and 5 cats with a histopathologically or cytologically confirmed nasal tumor were retrospectively reviewed. The level of suspicion for nasal neoplasia after CT and/or rhinoscopy was compared to the definitive diagnosis. Twelve animals underwent CT, 14 underwent rhinoscopy, and 4 both examinations. Of the 12 CT examinations performed, 11 (92%) resulted in the conclusion that a nasal tumor was the most likely diagnosis compared with 9/14 (64%) for rhinoscopies. Computed tomography appeared to be more reliable than rhinoscopy for detecting nasal tumors and should therefore be considered as the first-line procedure.


Examen de première intention lors de suspicion de tumeur nasale: scanner où rhinoscopie? Une étude pilote. Lors de suspicion de tumeur nasale chez le chien et le chat, il n'existe à ce jour aucun consensus quant à l'examen de première intention à privilégier entre la tomodensitométrie et l'endoscopie lorsqu'un seul examen peut être réalisé. Les caractéristiques tomodensitométriques et endoscopiques de 17 chiens et 5 chats avec un diagnostic de tumeur nasale confirmé histologiquement ou cytologiquement ont été analysées rétrospectivement. Le degré de suspicion de tumeur nasale permis par l'endoscopie et/ou le scanner a été comparé au diagnostic final. Un examen tomodensitométrique a été réalisé chez 12 animaux, une rhinoscopie chez 14 et les deux examens ont été couplés dans quatre cas. L'examen scanner a conclu qu'une tumeur nasale était le diagnostic le plus probable dans 11 cas sur 12 (92 %), et la rhinoscopie dans 9 cas sur 14 (64 %). L'examen scanner apparait plus fiable que la rhinoscopie pour détecter les tumeurs nasales, et de ce fait devrait être considéré comme le meilleur examen de première intention.(Traduit par les auteurs).


Asunto(s)
Carcinoma/veterinaria , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Perros/diagnóstico , Neoplasias Nasales/veterinaria , Sarcoma/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Animales , Carcinoma/clasificación , Carcinoma/diagnóstico , Gatos , Perros , Femenino , Masculino , Neoplasias Nasales/diagnóstico , Proyectos Piloto , Sarcoma/diagnóstico
17.
J Neurosci Methods ; 221: 159-65, 2014 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-24126047

RESUMEN

The prognosis of glioblastoma remains poor despite significant improvement in cytoreductive surgery, external irradiation and new approach of systemic treatment as antiangiogenic therapy. One of the issues is the low concentration in the infiltrated parenchyma of therapeutic agent administered intravenously mainly due to the blood-brain barrier. An intracerebral injection is advocated to overpass this barrier, this kind of administration need a low flow and continuous injection. The development of sophisticated implanted devices for convection-enhanced delivery is a mandatory step to have a controlled released of a therapeutic agent in glioblastoma treatment. Before testing such a device in a clinical trial a serious preclinical studies are required, in order to test it in realistic conditions we have develop the first induced high grade glioma model in a non-rodent animal: the pig. 21 pigs have been implanted in the parietal lobe with human glioblastoma cell lineage under a chemical immunosuppression by ciclosporine. A MRI follow up was then realized. 15 pigs have been implanted with U87MG, 14 have presented a macroscopic significant tumor, with radiological and anatomapathological characteristics of high grade glioma. 6 pigs were implanted with G6, stem-like cells tumors of glioblastoma, 1 pig develops a macroscopic tumor. This is the first reproducible glioma model in a large animal described, it open the way to preclinical studies to test implanted devices in anatomic realistic conditions, without the ethical issues of a primate use.


Asunto(s)
Neoplasias Encefálicas/patología , Línea Celular Tumoral/trasplante , Modelos Animales de Enfermedad , Glioma/patología , Animales , Xenoinjertos , Humanos , Imagen por Resonancia Magnética , Sus scrofa
18.
Cancer Lett ; 334(2): 188-95, 2013 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-23200675

RESUMEN

We investigated how near-infrared imaging could improve highly infiltrative spontaneous fibrosarcoma surgery in 12 cats in a clinical veterinary phase. We used an RGD-based nanoprobe at different doses and times before surgery and a portable clinical grade imaging system. All tumours were labelled by the tracer and had an overall tumour-to-healthy tissue ratio of 14±1 during surgery. No false negatives were found, and the percentage of tumour cells was linearly correlated with the fluorescence intensity. All cats recovered well and were submitted to long-term follow-up that is currently on-going 1year after the beginning of the study.


Asunto(s)
Enfermedades de los Gatos/cirugía , Fibrosarcoma/veterinaria , Integrina alfaVbeta3/análisis , Animales , Enfermedades de los Gatos/metabolismo , Gatos , Femenino , Fibrosarcoma/metabolismo , Fibrosarcoma/radioterapia , Fibrosarcoma/cirugía , Técnica del Anticuerpo Fluorescente/métodos , Técnica del Anticuerpo Fluorescente/veterinaria , Aumento de la Imagen/métodos , Integrina alfaVbeta3/metabolismo , Masculino , Sondas Moleculares , Espectroscopía Infrarroja Corta/métodos , Espectroscopía Infrarroja Corta/veterinaria , Distribución Tisular
19.
J Vet Diagn Invest ; 20(6): 824-6, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18987239

RESUMEN

A case of presumed primary muscular lymphoma in an 8-year-old, intact, male Newfoundland dog is reported. The dog was presented for evaluation of an infiltrating ventral cervical mass, respiratory distress, and anorexia of 1-month duration. Fine-needle aspiration of the mass revealed anaplastic large cell lymphoma. Despite chemotherapy, health status declined and the animal was euthanized a few weeks later. At necropsy, the mass infiltrated the cervical muscles and extended ventrally to the left forelimb and cranially to the tongue and laryngeal musculature. Other muscles were infiltrated by the same neoplasm (diaphragm and intercostal, abdominal, and gluteal muscles) indicating a probable multicentric origin. Histological examination confirmed the diagnosis of anaplastic large cell lymphoma, which showed a strong muscular tropism. Immunohistochemical staining revealed neoplastic cell reactivity for cluster of differentiation 3 (CD3) and Ki-67 antigens (70% and 90%, respectively). The neoplastic cells were negative for CD79a. The presumed histological diagnosis in this dog was primary muscular anaplastic large T-cell lymphoma.


Asunto(s)
Enfermedades de los Perros/patología , Linfoma/veterinaria , Neoplasias de los Músculos/veterinaria , Animales , Autopsia , Biopsia con Aguja Fina/métodos , Biopsia con Aguja Fina/veterinaria , Perros , Eutanasia , Linfocitos/patología , Linfoma/patología , Masculino , Neoplasias de los Músculos/patología
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