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Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas. This review includes information on the signalment, presentation, etiopathogenesis, classification, histologic and immunohistochemical diagnosis, clinical management, and biochemical and genetic derangements of canine follicular and medullary carcinomas, and their correlates with human medicine.
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Adenocarcinoma Folicular , Carcinoma Medular , Carcinoma Neuroendócrino , Doenças do Cão , Neoplasias da Glândula Tireoide , Humanos , Cães , Animais , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/veterinária , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/veterinária , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/veterinária , Carcinoma Medular/patologia , Carcinoma Medular/veterinária , Doenças do Cão/diagnósticoRESUMO
153 Sm-DOTMP (CycloSam® ) is a newly-patented radiopharmaceutical for bone tumor treatment. DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate) is a macrocyclic chelating agent with superior binding properties to 153 Sm when compared with EDTMP (Quadramet™, used for palliative treatment of bone cancer). CycloSam® was administered at 1 mCi/kg (37 MBq/kg) in a prospective pilot study to seven dogs with bone cancer resulting in no myelosuppression. Then, 13 dogs were enrolled in a prospective clinical trial study using traditional 3+3 dose escalation and starting at 1.5 mCi/kg. Baseline evaluation included hematologic and biochemical testing, diagnosis confirmation, thoracic and limb radiographs, technetium-99 m-HDP bone scintigraphy, and 18 F-FDG PET scan (SUVmax). Toxicity (primary endpoint) was assessed through weekly blood counts and adverse events. Dogs received 1.5 mCi/kg (n = 4), 1.75 mCi/kg (n = 6), and 2 mCi/kg (n = 3) of 153 Sm-DOTMP. Dose-limiting neutropenia and thrombocytopenia were seen at 2 mCi/kg. No dose-limiting nonhematologic toxicities occurred. Efficacy (secondary endpoint) was assessed by objective lameness measurement (body-mounted inertial sensors), owner quality-of-life (QoL) questionnaire, and repeat PET scan. Objective lameness measurement improved in four dogs (53%-60% decrease) was equivocal in three dogs, and worsened in four dogs (66%-115% increase); two dogs were not evaluable. Repeat 18 F-FDG PET scan results varied and change in lameness did not consistently correlate with SUVmax changes. QoL score worsened (n = 5) or was improved/stable (n = 7). Carboplatin chemotherapy (300 mg/m2 IV every 3 weeks ×4) started 4 weeks after 153 Sm-DOTMP injection. No dog died of chemotherapy-related complications. All dogs completed study monitoring. The recommended dose for CycloSam® in dogs is 1.75 mCi/kg, which resulted in some pain control with minimal toxicity and was safely combined with chemotherapy.
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Antineoplásicos , Neoplasias Ósseas , Doenças do Cão , Osteossarcoma , Compostos Radiofarmacêuticos , Animais , Cães , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Fluordesoxiglucose F18 , Coxeadura Animal/diagnóstico por imagem , Coxeadura Animal/tratamento farmacológico , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/veterinária , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Samário/efeitos adversosRESUMO
Osteochondrodysplasia is a painful, progressive clinical syndrome unique to Scottish fold cats because of a heritable missense mutation in the TRPV4 gene. An 8 yr old male neutered Scottish fold cat was presented for a mass on his hind paw. The mass caused decreased mobility in the metatarsal region and digits and resulted in significant discomfort. Because of extensive skeletal abnormalities attributed to breed-related osteochondrodysplasia, the owner was reluctant to pursue amputation. Radiation therapy was pursued for palliation of pain. After coarsely fractionated external beam radiotherapy resulted in stabilization of the mass with eventual progression after 14 mo, samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid was administered systemically, and the cat showed immediate, whole-body improvement in mobility. Concurrent intestinal and respiratory disease was evaluated and managed. Samarium-153-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid administration was repeated approximately every 6 mo for three treatments until the cat succumbed to thromboembolic disease attributed to previously diagnosed cardiac disease. Radiation therapy administered using either external beam or bone-seeking radioisotopes can be effective at palliating clinical signs associated with the skeletal abnormalities that accompany this disease.
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Doenças do Gato/terapia , Compostos Organofosforados/uso terapêutico , Osteocondrodisplasias/veterinária , Radioisótopos/uso terapêutico , Samário/uso terapêutico , Animais , Gatos , Masculino , Compostos Organofosforados/química , Osteocondrodisplasias/tratamento farmacológico , Osteocondrodisplasias/radioterapia , Radioisótopos/química , Samário/química , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. We aim here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. We use tissue engineering approaches to recreate the three-dimensional tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient derived xenograft GBM cells. We reveal that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype dependent manner. We propose a tumor specific combination treatment of HYAL and HAS inhibitors to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand - dependent signaling roles of hyaluronan in glioblastoma. Significance: The control of aberrant hyaluronan metabolism in the tumor microenvironment can improve the efficacy of current treatments. Bioengineered preclinical models demonstrate potential to predict, stratify and accelerate the development of cancer treatments.
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PURPOSE: Interleukin-2 and -12 cytokines have potent anti-cancer activity, but suffer a narrow therapeutic window due to off-tumor immune cell activation. Engineering cytokines with the ability to bind and associate with tumor collagen after intratumoral injection potentiated response without toxicity in mice, and was previously safe in pet dogs with sarcoma. Here we sought to test the efficacy of this approach with in dogs with advanced melanoma. EXPERIMENTAL DESIGN: This study examined fifteen client-owned dogs with histologically- or cytologically-confirmed malignant melanoma who received a single 9 Gray fraction of radiation therapy, followed by six cycles of combined collagen-anchored IL-2 and IL-12 therapy Q2W. Cytokine dosing followed a 3+3 dose escalation design, with the initial cytokine dose chosen from prior evaluation in canine sarcomas. No exclusion criteria for tumor stage or metastatic burden, age, weight, or neuter status were applied for this trial. RESULTS: Median survival regardless of tumor stage or dose level was 256 days and 10/13 (76.9%) dogs that completed treatment had CT-measured tumor regression at the treated lesion. In dogs with metastatic disease, 8/13 (61.5%) dogs had partial responses across their combined lesions, evidence of locoregional response. Profiling by Nanostring of treatment-resistant dogs revealed that B2m loss was predictive of poor response to this therapy. CONCLUSIONS: Collectively, these results confirm the ability of locally administered tumor-anchored cytokines to potentiate responses at regional disease sites when combined with radiation. This evidence supports the clinical translation of this approach and highlights the utility of comparative investigation in canine cancers.
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BACKGROUND: Paclitaxel is an effective antimitotic agent in cancer treatment; however, one of its most common toxicities is hypersensitivity due to excipients used for water solubility. Nanoparticulate paclitaxel (Crititax®, CTI52010) is paclitaxel that consists only of nanoparticulate drug in saline. Our objective was to examine the effect of nanoparticulate paclitaxel on prostate cancer cells derived from castration-resistant prostate cancer in men and dogs, as companion dogs represent a unique naturally occurring model of castration-resistant prostate cancer. We hypothesized that nanoparticulate paclitaxel would be effective in affecting cell viability, colony forming ability, apoptosis, and induction of structural changes to the microtubules of prostate cancer cells. METHODS: Human PC3 and canine Ace-1 cells were treated with 0.001-1.0 µm concentrations of paclitaxel and nanoparticulate paclitaxel. Cell viability, apoptosis, and colony forming assays were analyzed and compared in the presence of both drugs. Microtubule structure was examined by fluorescence microscopy following incubation with drug. RESULTS: Nanoparticulate paclitaxel was as effective as standard paclitaxel in decreasing cell viability, decreasing colony forming ability, and inducing apoptosis in human and canine prostate cancer cells in a dose-dependent manner. Fluorescence microscopy confirmed the microtubule target of nanoparticulate paclitaxel. CONCLUSIONS: Nanoparticulate paclitaxel is as effective as paclitaxel in decreasing cell viability, initiating apoptosis, decreasing cell survival, and causing rigidity of microtubules in both human and canine castration-resistant prostate cancer. This represents an attractive area for further study, using the companion dog as a model for disease in men.
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Antineoplásicos Fitogênicos/farmacologia , Nanopartículas , Paclitaxel/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cães , Humanos , MasculinoRESUMO
Feline oral squamous cell carcinoma (FOSCC) is the most common oral tumour diagnosed in pet cats and carries a poor prognosis with <10% one-year survival despite multi-modal therapies. Tumours of the mandible or maxilla are frequently osteo-invasive and pain can result from osteolysis. Zoledronate is a bisphosphonate that inhibits osteoclasts and reduces bone resorption. Radiation therapy (RT) is used to treat FOSCC due to anti-cancer activity and ability to improve quality of life. We hypothesized RT can be safely combined with zoledronate, and that this combinatory therapy would be efficacious, well tolerated, and result in decreased bone resorption in cats with FOSCC. SCCF1 cell line was treated with zoledronate before, concurrently, or after RT, and clonogenic assays were performed to determine if an optimal dosing schedule would be identified. Nine cats with osteoinvasive FOSCC were recruited for treatment with 4 weekly doses of 8 Gy RT combined with zoledronate administered at the first and fourth treatments. Serial CT scans were performed to assess tumour response. Safety and tolerability were monitored with hematologic and biochemical parameters, and acute radiation effects were characterized. Serum c-telopeptide (CTx) and relative bone mineral density (rBMD) by dual -energy X-ray absorptiometry (DEXA) quantified bone resorption. In vitro studies showed no clear benefit to timing of zoledronate with RT, therefore all zoledronate was administered concurrently with RT in FOSCC patients. Based on tumour volume, 4/9 (44.4%) cats achieved partial remission, 4/9 (44.4%) stable disease and 1/9 (11.1%) had progressive disease. The combinatory therapy was well-tolerated based on biochemical measurements, and all patients experienced decreased serum CTx. Combining RT with zoledronate in tumour-bearing cats is safe, well-tolerated, results in a partial remission rate of up to 44%, and decreases serum CTx, a marker of bone resorption.
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Conservadores da Densidade Óssea , Carcinoma de Células Escamosas , Doenças do Gato , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Osteólise , Gatos , Animais , Ácido Zoledrônico/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/radioterapia , Neoplasias Bucais/veterinária , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/veterinária , Qualidade de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/veterinária , Difosfonatos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteólise/tratamento farmacológico , Osteólise/veterinária , Neoplasias de Cabeça e Pescoço/veterinária , Doenças do Gato/tratamento farmacológico , Doenças do Gato/radioterapiaRESUMO
OBJECTIVE: To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. DESIGN: Retrospective case series. ANIMALS: 95 dogs with lymphoma. PROCEDURES: Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. RESULTS: Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Cães , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Esquema de Medicação , Linfoma/tratamento farmacológico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
A retrospective epidemiologic study evaluated 1,129 feline intestinal tumor patients via data entered into the Veterinary Medical Database (VMDB) from 1964 to 2004. Cases were analyzed by breed, age, yr of diagnosis, tumor type, and location. The VMDB incidence of all intestinal tumors reported during this 40 yr period was 0.4%, with small intestinal tumors predominating. The most common intestinal tumor was lymphoma, but the most common nonlymphoid tumor was adenocarcinoma. The Siamese breed and increasing age after 7 yr conferred an increased risk. Intact males and females appeared to have a decreased risk compared with neutered patients, but this may be explained by the age difference among these patients as older patients were more likely to be neutered. Prospective studies evaluating neuter status predilection and prognosis are warranted.
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Doenças do Gato/epidemiologia , Neoplasias Intestinais/veterinária , Adenocarcinoma/epidemiologia , Adenocarcinoma/veterinária , Fatores Etários , Animais , Castração/veterinária , Gatos , Feminino , Incidência , Neoplasias Intestinais/epidemiologia , Linfoma/epidemiologia , Linfoma/veterinária , Masculino , Prognóstico , Estudos Retrospectivos , Fatores SexuaisRESUMO
Objective: To identify the effect of glutathione (GSH) on cell survival in a novel in vitro model of itraconazole (ITZ)-associated hepatotoxicity using canine primary hepatocytes. Sample: Commercially sourced, cryopreserved male dog (Beagle) primary hepatocytes from a single donor. Procedures: Using a sandwich culture technique, canine primary hepatocytes were exposed to serial dilutions of ITZ. Calcein AM, 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and neutral red were investigated as potential cell viability assays. Hepatocytes were then pre-incubated with GSH, exposed to serial dilutions of ITZ, and cell viability determined at 4 and 24 h post-ITZ exposure. Each condition was performed in technical triplicate and the effect of time, GSH concentration, and ITZ concentration on % cytotoxicity assessed using a multivariate linear regression model. Tukey's post-hoc test was used to detect individual differences. Results: The neutral red cell cytotoxicity assay was chosen based on its superior ability to detect dose-dependent changes in viability. Hepatocyte cytotoxicity significantly increased with ITZ concentration (P < 0.001) and time (P = 0.004) and significantly decreased with GSH treatment (P < 0.001). Conclusions and Clinical Relevance: This in vitro model demonstrates dose- and time-dependent ITZ-induced cytotoxicity, which is similar to clinical changes observed in canine patients and in in vivo rodent studies. Pre-treating with GSH is protective against in vitro cell death. These results suggest that GSH precursors may have a role in the management or prevention of ITZ-associated hepatotoxicity in dogs. Clinical trials are needed to evaluate their utility for this adverse drug reaction.
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Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies.
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Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Terapia de Alvo Molecular , Neoplasias Bucais/metabolismo , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , Animais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Gatos , Terapia Combinada , Gerenciamento Clínico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Imuno-Histoquímica , Camundongos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/etiologia , Mutação , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Polimorfismo de Nucleotídeo Único , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The therapeutic efficacy of drugs is dependent upon the ability of a drug to reach its target, and drug penetration into tumors is limited by abnormal vasculature and high interstitial pressure. Chemotherapy is the most common systemic treatment for cancer but can cause undesirable adverse effects, including toxicity to the bone marrow and gastrointestinal system. Therefore, nanotechnology-based drug delivery systems have been developed to reduce the adverse effects of traditional chemotherapy by enhancing the penetration and selective drug retention in tumor tissues. A thorough knowledge of the physical properties (e.g., size, surface charge, shape, and mechanical strength) and chemical attributes of nanoparticles is crucial to facilitate the application of nanotechnology to biomedical applications. This review provides a summary of how the attributes of nanoparticles can be exploited to improve therapeutic efficacy. An ideal nanoparticle is proposed at the end of this review in order to guide future development of nanoparticles for improved drug targeting in vivo.
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A medulloblastoma was surgically debulked from a 6 year old American Staffordshire Terrier, who then received a modified lomustine (CCNU), vincristine, procarbazine, and prednisolone (LOPP) protocol. The dog improved significantly and continued to do well until deterioration and euthanasia 5 months following surgery. This is the first known published case report of surgical cytoreductive surgery of a medulloblastoma in a dog with documented response to surgery and chemotherapy. Medulloblastoma is a primitive neuroectodermal tumor that is the most common malignant central nervous system (CNS) tumor in children, though it is less common in adults. This case illustrates the value of considering human literature when creating treatment plans for uncommon brain tumors in veterinary patients. Medulloblastoma should be a differential for cerebellar tumors in young to middle aged dogs, and surgery and chemotherapy should be considered.
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BACKGROUND: Body surface area (BSA) can reflect metabolic rate that might normalize dosing of chemotherapeutics across widely variable weights within a species. The current BSA formula for dogs lacks height, length, and body condition. HYPOTHESIS: Computed tomography (CT) imaging will allow inclusion of morphometric variables in allometric modeling of BSA in dogs resulting in an improved formula for BSA estimation. ANIMALS: Forty-eight dogs from 4 institutions with whole-body CT images. METHODS: Retrospective and prospective case series. Body surface area was contoured using whole-body CT scans and radiation therapy planning software. Body length and height were determined from CT images and also in 9 dogs by physical measurement. Nonlinear regression was used to model the BSA data sets using allometric equations. Goodness-of-fit criteria included average relative deviation, mean standard error, Akaike information criterion, and r2 (derived from the r-value generated by regression models). RESULTS: Contoured BSA differed from the current formula by -9% to +19%. Nonlinear regression on untransformed data yielded BSA = 0.0134 × body weight [kg]⧠0.4746 × length (cm)⧠0.6393 as the best-fit model. Heteroscedasticity (increasing morphometric variability with increasing BSA) was an important finding. CONCLUSIONS AND CLINICAL IMPORTANCE: Computed tomography-derived BSA was used to incorporate body length into a novel BSA formula. This formula can be applied prospectively to determine whether it correlates with adverse events attributed to chemotherapy.
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Superfície Corporal/veterinária , Cães/anatomia & histologia , Tomografia Computadorizada por Raios X/métodos , Animais , Peso Corporal , Feminino , Masculino , Estudos Prospectivos , Análise de Regressão , Estudos Retrospectivos , SoftwareRESUMO
BACKGROUND: Canine osteosarcoma (OS) is a relevant spontaneous model for human OS. Identifying similarities in clinical characteristics associated with metastasis at diagnosis in both species may substantiate research aimed at using canine OS as a model for identifying mechanisms driving distant spread in the human disease. METHODS: This retrospective study included dog OS cases from three academic veterinary hospitals and human OS cases from the Surveillance, Epidemiology, and End Results program. Associations between clinical factors and metastasis at diagnosis were estimated using logistic regression models. RESULTS: In humans, those with trunk tumors had higher odds of metastasis at diagnosis compared to those with lower limb tumors (OR = 2.38, 95% CI: 1.51, 3.69). A similar observation was seen in dogs with trunk tumors compared to dogs with forelimb tumors (OR = 3.28, 95% CI 1.36, 7.50). Other associations were observed in humans but not in dogs. Humans aged 20-29 years had lower odds of metastasis at diagnosis compared to those aged 10-14 years (OR = 0.67, 95% CI: 0.47, 0.96); every 1-cm increase in tumor size was associated with a 6% increase in the odds of metastasis at diagnosis (95% CI: 1.04, 1.08); compared to those with a white, non-Hispanic race, higher odds were observed among those with a black, non-Hispanic race (OR: 1.51, 95% CI: 1.04, 2.16), and those with a Hispanic origin (OR 1.35, 95% CI: 1.00, 1.81). CONCLUSION: A common mechanism may be driving trunk tumors to progress to detectable metastasis prior to diagnosis in both species.
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Neoplasias Ósseas/diagnóstico , Doenças do Cão/diagnóstico , Osteossarcoma/diagnóstico , Animais , Neoplasias Ósseas/etiologia , Doenças do Cão/etiologia , Cães , Feminino , Humanos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Osteossarcoma/etiologia , Fatores de Risco , Programa de SEER , Carga TumoralRESUMO
Carriers used to solubilize taxane chemotherapy drugs cause severe hypersensitivity. Nanoparticle formulations can provide improved dissolution and bioavailability of taxanes. Thus, a nanoparticulate, excipient-free formulation of paclitaxel (CTI52010) was evaluated in tumour-bearing dogs with intravenous and subcutaneous delivery. Tumour-bearing dogs were treated with intravenous CTI52010 using a modified rapid dose escalation scheme. Subcutaneous administration was then planned for a small cohort of dogs for comparison. For both groups, serial blood samples were collected after first dosing for pharmacokinetic analysis by LCMSMS. Tumour response was measured using RECIST criteria. Toxicity was recorded using VCOG-CTCAEv1.1. Fifteen dogs were treated with intravenous delivery at increasing dosages (80-136 mg/m2 ), with one objective response in the urethral component of a prostatic carcinoma (probable transitional cell carcinoma) and four dogs with durable stable disease (two carcinomas, two sarcomas). Pharmacokinetic data indicate a rapid initial clearing of the drug from serum followed by an extended elimination half-life, similar to normal dogs and suggesting reticuloendothelial clearance. Parameters and toxicity were highly variable and a maximally tolerated dosage could not be reliably confirmed. Three dogs were treated with subcutaneous delivery and no drug was detected in circulation, resulting in termination of the study. This novel formulation of paclitaxel is well tolerated in dogs and no unique toxicity or hypersensitivity was noted. The preliminary responses suggest biologic activity. The lack of systemic absorption after subcutaneous administration suggests a possible role for intratumoural anticancer therapy.
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Antineoplásicos Fitogênicos/administração & dosagem , Doenças do Cão/tratamento farmacológico , Recidiva Local de Neoplasia/veterinária , Paclitaxel/administração & dosagem , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Cães , Esquema de Medicação/veterinária , Feminino , Infusões Intravenosas/veterinária , Injeções Subcutâneas/veterinária , Masculino , Nanopartículas/administração & dosagem , Nanopartículas/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/efeitos adversos , Paclitaxel/farmacocinética , Paclitaxel/uso terapêuticoAssuntos
Doenças do Cão , Melanoma , Animais , Doenças do Cão/terapia , Cães , Imunoterapia/veterinária , Melanoma/terapia , Melanoma/veterináriaRESUMO
OBJECTIVE: To determine the effect of dietary n-3 fatty acids on the pharmacokinetics of doxorubicin in dogs with lymphoma. ANIMALS: 23 dogs with lymphoma in stages IIIa, IVa, and Va. PROCEDURE: Dogs receiving doxorubicin chemotherapy were randomly allocated to receive food with a high (test group) or low (control group) content of n-3 fatty acids. Serum doxorubicin and doxorubicinol concentrations were measured via high-performance liquid chromatography before and 6 to 9 weeks after initiation of the diets. Lymph node concentrations of doxorubicin were assessed 6 hours after the initial treatment. Dogs' body composition was assessed by means of dual-energy x-ray absorptiometry scans. RESULTS: No significant differences in doxorubicin pharmacokinetics were detected between treatment groups. Significant differences existed between the first and second sampling times among all dogs for area under the curve, maximum serum concentration, and clearance. Differences in body composition did not affect measured pharmacokinetic variables. The terminal elimination half-life was longer in dogs in which a long-term remission was achieved than in dogs that did not have remission. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary supplementation of n-3 fatty acids is common in veterinary patients with neoplasia, but supplementation did not affect doxorubicin pharmacokinetics in this population of dogs. Explanations for the beneficial effects of n-3 fatty acids other than alterations in the pharmacokinetics of chemotherapy drugs should be investigated. Dogs may metabolize drugs differently prior to remission of lymphoma than when in remission. The pharmacokinetics of doxorubicin at the time of the first administration may predict response to treatment.
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Suplementos Nutricionais , Doenças do Cão/metabolismo , Doxorrubicina/farmacocinética , Ácidos Graxos Ômega-3/metabolismo , Linfoma/veterinária , Animais , Cromatografia Líquida de Alta Pressão , Doenças do Cão/tratamento farmacológico , Cães , Doxorrubicina/sangue , Doxorrubicina/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Meia-Vida , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Fatores de TempoRESUMO
Medical records for 67 cats with histologically confirmed mammary gland adenocarcinomas treated with adjunctive doxorubicin from June 1994 through December 2002 were reviewed. Data were examined to evaluate factors influencing disease-free interval (DFI) and survival time. The Kaplan-Meier median survival time of cats that received surgery and doxorubicin was 448 days. The Kaplan-Meier median DFI was 255 days. Significant univariate prognostic factors for DFI included histological subtype, completion of initial chemotherapy, development of metastatic disease, and location of metastatic disease. Significant univariate prognostic factors for survival included tumor volume, the development of metastatic disease, and location of metastatic disease.
Assuntos
Adenocarcinoma/veterinária , Antibióticos Antineoplásicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Doxorrubicina/uso terapêutico , Neoplasias Mamárias Animais/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Animais , Doenças do Gato/mortalidade , Doenças do Gato/patologia , Gatos , Intervalo Livre de Doença , Feminino , Estimativa de Kaplan-Meier , Masculino , Neoplasias Mamárias Animais/mortalidade , Neoplasias Mamárias Animais/patologia , Metástase Neoplásica , Estadiamento de Neoplasias/veterinária , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the effect of adjuvant doxorubicin chemotherapy on outcome in dogs with high-grade (grade 3) soft tissue sarcomas (HGSTSs). DESIGN: Retrospective case series. ANIMALS: 39 dogs. PROCEDURES: Medical records of dogs with HGSTSs were reviewed. Dogs treated with surgery alone or receiving single-agent doxorubicin chemotherapy postoperatively were included in the study. Owners and referring veterinarians were contacted for follow-up information. Slides from histologic sections were reviewed to confirm the diagnosis of HGSTSs. Cases in which follow-up examination was not performed and radiation therapy or chemotherapy other than doxorubicin was administered were excluded. RESULTS: 39 dogs met inclusion criteria. Twenty-one dogs received adjuvant doxorubicin. Tumor-, patient-, and treatment-related variables were not significantly associated with measured outcomes including local, metastatic, and overall disease-free intervals as well as survival time. Overall median disease-free interval was 724 days with a median survival time of 856 days for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Adjuvant doxorubicin-based chemotherapy did not benefit this population of dogs with HGSTSs. Outcome for visceral HGSTSs was similar to that of nonvisceral HGSTSs in these cases.