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1.
Vet Pathol ; : 3009858241257897, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842063

RESUMO

Myeloid sarcoma (MS) is a solid tumor of granulocytic origin with extramedullary localization. This tumor is rare in humans and animals. The diagnostic approach is heterogeneous, and the definitive diagnosis may be difficult to achieve. Primary MS has never been described as a spontaneous neoplasm in companion dogs. Two purebred and 1 mixed-breed dogs, 6- to 11-year-old, developed round cell tumors in the mediastinum, lymph nodes (LNs) and tonsils, and LNs, respectively. Granulocytic origin and exclusion of lymphoid lineage were confirmed by flow cytometry, supported by immunohistochemistry or immunocytochemistry. Pivotal to the diagnosis were positive labeling for myeloid (CD11b, CD14) and hematopoietic precursors (CD34) markers, along with negative labeling for lymphoid markers. Blood and bone marrow infiltration were not detected at initial diagnosis, excluding acute myeloid leukemia. The behavior of these tumors was aggressive, resulting in poor clinical outcomes, even when chemotherapy was attempted.

2.
Vet Pathol ; : 3009858241244853, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613423

RESUMO

Canine oral malignant melanoma (COMM) is the most common neoplasm in the oral cavity characterized by local invasiveness and high metastatic potential. Hypoxia represents a crucial feature of the solid tumor microenvironment promoting cancer progression and drug resistance. Hypoxia-inducible factor-1α (HIF-1α) and its downstream effectors, vascular endothelial growth factor A (VEGF-A), glucose transporter isoform 1 (GLUT1), C-X-C chemokine receptor type 4 (CXCR4), and carbonic anhydrase IX (CAIX), are the main regulators of the adaptive response to low oxygen availability. The prognostic value of these markers was evaluated in 36 COMMs using immunohistochemistry. In addition, the effects of cobalt chloride-mediated hypoxia were evaluated in 1 primary COMM cell line. HIF-1α expression was observed in the nucleus, and this localization correlated with the presence or enhanced expression of HIF-1α-regulated genes at the protein level. Multivariate analysis revealed that in dogs given chondroitin sulfate proteoglycan-4 (CSPG4) DNA vaccine, COMMs expressing HIF-1α, VEGF-A, and CXCR4 were associated with shorter disease-free intervals (DFI) compared with tumors that were negative for these markers (P = .03), suggesting hypoxia can influence immunotherapy response. Western blotting showed that, under chemically induced hypoxia, COMM cells accumulate HIF-1α and smaller amounts of CAIX. HIF-1α induction and stabilization triggered by hypoxia was corroborated by immunofluorescence, showing its nuclear translocation. These findings reinforce the role of an hypoxic microenvironment in tumor progression and patient outcome in COMM, as previously established in several human and canine cancers. In addition, hypoxic markers may represent promising prognostic markers, highlighting opportunities for their use in therapeutic strategies for COMMs.

3.
Vet Comp Oncol ; 22(2): 198-203, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38327132

RESUMO

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi-institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow-up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty-six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow-up, resulting in an overall metastatic rate of 30%. Forty-nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour-specific survival (TSS) were not reached. One- and 2-year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1- and 2-year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P < .001) and TSS (P = .001) compared with non-operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour-related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain.


Assuntos
Doenças do Gato , Osteossarcoma , Animais , Osteossarcoma/veterinária , Osteossarcoma/terapia , Osteossarcoma/patologia , Gatos , Doenças do Gato/patologia , Estudos Retrospectivos , Masculino , Feminino , Neoplasias Ósseas/veterinária , Neoplasias Ósseas/patologia , Neoplasias do Apêndice/veterinária , Neoplasias do Apêndice/patologia , Itália
4.
Vet Sci ; 10(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37624282

RESUMO

Hematological indices play a prognostic role in human osteosarcoma (OSA), but data are limited in dogs. The aim of this retrospective multicentric cohort study was to investigate the prognostic significance of pre-operative hematological/inflammatory indices in a cohort of client-owned dogs with appendicular OSA receiving standardized treatment. Cut-offs associated with progression-free survival (PFS) for pre-operative hematological values/ratios were established using the minimal p-value approach. Historical prognostic factors were also assessed. Statistical analyses were performed for the whole population and after the exclusion of sighthounds. Fifty-nine dogs were included (13 were sighthounds). Multivariable analysis revealed that a low neutrophil count (<4.37 × 109/L, HR0.28, CI 95% 0.13-0.61, p = 0.001), a high red blood cell count (≥7.91, HR3.5, CI 95% 1.56-7.9, p = 0.002), and a proximal humerus location (HR3.0, CI 95% 1.48-6.1, p = 0.002) were associated with shorter PFS. In the sighthound-only population, only OSA location was significantly associated with PFS in univariable analysis. When sighthounds were excluded, a low neutrophil count, a low monocyte count, and a proximal humerus location were associated with shorter PFS, in multivariable analysis. Neutrophil count and possibly monocyte and red blood cell counts can be useful prognostic markers in canine OSA treated with amputation and adjuvant carboplatin. However, not all indices are appropriate in sighthounds.

5.
Vet Sci ; 10(7)2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37505841

RESUMO

Several studies evaluating Ki67 in canine cutaneous mast cell tumors (cMCTs) have reported its prognostic value when tumors of all histological grades are included. This study aims to evaluate whether the Ki67 index has a predictive value in a homogeneous cohort of G2/LG cMCTs with HN2 lymph nodes (LNs) and to describe the clinical outcome. The second goal was to explore the correlation between the Ki67 index and MC. The medical databases of three institutions were retrospectively searched for dogs undergoing surgical treatment for cMCT and LN extirpation, with a histological diagnosis of G2/LG with HN2 LNs. Information about histological margins, MC, Ki67 index, local recurrence, nodal relapse, distant metastasis, de novo cMCT occurrence and date and cause of death were included. A total of 39 cases were identified. None of these developed local and nodal relapse or metastatic distant disease. Median MC was 1 (0-2). Median Ki67 index was 3.5 (0.7-14.3). Ki67 and MC were not significantly correlated. At the end of the study, 32 (82%) dogs were alive, 7 (18%) dogs were dead from unrelated causes and 4 (10.2%) dogs were lost to follow-up. The median ST was not reached, and the mean was 893 days (104-2241 days). Considering the strict inclusion criteria, dogs affected by G2/LG with HN2 LNs treated with surgery alone may have a good oncologic outcome; the Ki67 index does not have prognostic impact.

6.
Mol Ther ; 31(8): 2342-2359, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37312451

RESUMO

The high mortality rate of osteosarcoma (OSA) patients highlights the requirement of alternative strategies. The young age of patients, as well as the rarity and aggressiveness of the disease, limits opportunities for the robust testing of novel therapies, suggesting the need for valuable preclinical systems. Having previously shown the overexpression of the chondroitin sulfate proteoglycan (CSPG)4 in OSA, herein the functional consequences of its downmodulation in human OSA cells were evaluated in vitro, with a significant impairment of cell proliferation, migration, and osteosphere generation. The potential of a chimeric human/dog (HuDo)-CSPG4 DNA vaccine was explored in translational comparative OSA models, including human xenograft mouse models and canine patients affected by spontaneous OSA. The adoptive transfer of HuDo-CSPG4 vaccine-induced CD8+ T cells and sera in immunodeficient human OSA-bearing mice delayed tumor growth and metastasis development. HuDo-CSPG4 vaccination resulted safe and effective in inducing anti-CSPG4 immunity in OSA-affected dogs, which displayed prolonged survival as compared to controls. Finally, HuDo-CSPG4 was also able to induce a cytotoxic response in a human surrogate setting in vitro. On the basis of these results and the high predictive value of spontaneous OSA in dogs, this study paves the way for a possible translation of this approach to humans.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Apneia Obstrutiva do Sono , Vacinas de DNA , Humanos , Cães , Animais , Camundongos , Linfócitos T CD8-Positivos , Proteoglicanas de Sulfatos de Condroitina , Osteossarcoma/genética , Osteossarcoma/terapia , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia , Vacinação
7.
Animals (Basel) ; 13(9)2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37174587

RESUMO

Saliva is an irritant of the subcutaneous tissue, thus causing the development of a non-epithelial reactive pseudocapsule. Metaplastic ossification of the pseudocapsule is a condition rarely described in the veterinary literature. The main causes of calcification are trauma, tumours, various chronic inflammatory conditions and fibrodysplasia ossificans progressiva. The aim of the present case series was to describe three dogs affected by a calcified salivary mucocele. The medical records of dogs affected by a cervical sialocele were retrospectively evaluated, and three cases met the inclusion criteria. All the dogs in this study were referred to the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Sciences of the University of Turin (Turin, Italy) for a large solid mass in the intermandibular region. The diagnosis of a mucocele was confirmed clinically by centesis and by radiography or CT. Complete excision of both the pseudocyst and the ipsilateral mandibular/monostomatic sublingual salivary gland was performed in all cases. The histological report showed large areas of bone metaplasia within the pseudocapsule and chronic sialadenitis. Based on this limited case series, complete excision of the pseudocyst and a concurrent sialoadenectomy provided an effective treatment for this rare salivary mucocele disorder.

8.
Vet Comp Oncol ; 21(2): 332-338, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36907653

RESUMO

Canine cutaneous mast cell tumours (cMCTs) of the pinna have been associated with an aggressive biological behaviour, although data remain scarce. The knowledge acquired over the past years on histologic gradings, and the value of lymph node (LN) staging, may help in better characterizing this anatomical presentation. The first aim was to describe the frequency, location, and histologic appearance of LN metastases in cMCT of the pinna. A second aim was to evaluate prognosis. Medical records of dogs with cMCT of the pinna, that underwent tumour and sentinel (SLN) or regional LN (RLN) excision, were reviewed. The influence of potential prognostic variables on time to progression (TTP) and tumour-specific survival (TSS) was investigated. Thirty-nine dogs were included: 19 (48.7%) had Kiupel high-grade (K-HG) and 20 (51.3%) had low-grade (K-LG) MCTs. Eighteen (46.1%) dogs underwent SLN mapping: the superficial cervical LN was at least one of SLN in 17 (94.4%) cases. Twenty-two (56.4%) dogs had LN metastases; the superficial cervical LN was always involved. On multivariable analysis, only K-HG was associated with increased risk of progression (p = .043) and tumour-related death (p = .021). Median TTP and TSS were 270 and 370 days in K-HG, respectively; these were not reached in dogs with K-LG tumours (p < .01). cMCTs of the pinna are often K-HG and are also associated with a higher frequency of LN metastasis; however, we confirmed the independent prognostic value of histologic grading. A multimodal treatment may lead to favourable long-term outcome. Moreover, the superficial cervical LN is most often the SLN.


Assuntos
Doenças do Cão , Mastocitoma Cutâneo , Cães , Animais , Estudos Retrospectivos , Doenças do Cão/patologia , Prognóstico , Mastocitoma Cutâneo/veterinária , Metástase Linfática
9.
J Vet Intern Med ; 37(2): 635-647, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36852498

RESUMO

BACKGROUND: Few studies have assessed predictors of outcome in dogs with thyroid tumors undergoing thyroidectomy. OBJECTIVE: To estimate the survival and identify prognostic factors in dogs with thyroid tumors treated by thyroidectomy. ANIMALS: A total of 144 client-owned dogs with thyroid neoplasia that underwent thyroidectomy. METHODS: Retrospective study. Data for analysis included hospital attended and year of surgery, signalment, thyroxine concentration, thyroid tumor features (lobe involvement, size, invasiveness, histopathological type), thrombosis, metastasis, additional surgery and therapy, administration of adjuvant chemotherapy. The association of predictors with survival (time from surgery to death) were assessed by calculating cause-specific hazard ratios (HRcs ) and 95% confidence intervals (CI). Causes of death were classified as thyroid-related or because of other cause. RESULTS: Overall median survival time was 802 days (CI95% = 723-1015 days); 89 dogs (77.4%) survived >500 days. Metastases were identified at admission in 12 (8.3%) dogs and were associated with higher thyroid cancer-related fatality (HR = 5.83, CI95% = 1.56-21.78; P = .009). Thrombosis occurred in 40 dogs and was associated with increased risk of death because of other cause (HR = 2.73, CI95% = 1.18-6.35; P = .019). Nonfollicular carcinoma (HR = 4.17, CI95% = 1.27-13.69; P = .018) and administration of chemotherapy (HR = 3.45, CI95% = 1.35-8.82; P = .01) were associated with higher risk of thyroid cancer-related death. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with thyroid tumors undergoing thyroidectomy have a long life expectancy. Despite the rare presence of nonfollicular carcinoma and metastases, thyroidectomy should still be considered in some of these dogs.


Assuntos
Carcinoma , Doenças do Cão , Neoplasias da Glândula Tireoide , Cães , Animais , Tireoidectomia/veterinária , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/veterinária , Análise de Sobrevida , Carcinoma/cirurgia , Carcinoma/veterinária , Prognóstico , Doenças do Cão/patologia
11.
Vet Comp Oncol ; 21(2): 208-220, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36635868

RESUMO

It is known that the regional lymph node (RLN) may not correspond to the sentinel lymph node (SLN) (the first lymph node draining the tumour), and many diagnostic techniques have recently been aimed at its detection. Although lymphoscintigraphy is the gold standard in both human and veterinary medicine for SLN mapping, it is relatively unavailable in veterinary medicine due to costs and difficult management of the radiotracer. This prospective study evaluated, as a first aim, the feasibility and sensitivity of the computed tomography lymphography (CTL) in detecting the SLN in 62 mast cell tumours (MCTs). The second aim was to evaluate the accuracy of the CTL in identifying the most representative lymph node of the patient's lymphatic status; the histological status of the SNL was compared with that of the RLN, to see in how many cases the patient's stage would have changed according to the RLN. When the RLN turned out to be also the SLN it was decided to excise, as a control LN, the one localised in the neighbourhood of the MCT (neighbouring lymph node; NLN). The detection rate was 90%, with failure of SLN identification in six cases. In 18 (32%) of 56 MCTs with a diagnostic CTL, the SLN did not correspond to the RLN. Forty-five MCTs were surgically removed, together with their corresponding SLN and RLN/NLN. Since the clinical stage of the patient would have changed in only 7% of cases, CTL is a reliable method of detecting the SLN and, for staging purposes, there is no need to remove other LNs.


Assuntos
Linfadenopatia , Linfonodo Sentinela , Humanos , Animais , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Linfografia/veterinária , Linfografia/métodos , Biópsia de Linfonodo Sentinela/veterinária , Biópsia de Linfonodo Sentinela/métodos , Estudos Prospectivos , Mastócitos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Tomografia Computadorizada por Raios X/veterinária , Linfadenopatia/patologia , Linfadenopatia/veterinária , Estadiamento de Neoplasias
12.
Animals (Basel) ; 13(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36670758

RESUMO

Compartmental excision consists of the complete resection of an anatomic district in which specific structures act as a barrier to local tumour invasion. It is a well-established procedure in human medicine, while only a few reports are available in veterinary medicine. The aim of this study was to describe complete muscle resection in 3 dogs affected by different intramuscular sarcomas. The clinical outcome was also reported. Medical records were searched, including preoperative diagnostic findings, compartmental excision, histologic diagnosis, and outcome. Three dogs fit the inclusion criteria, which had a sarcoma confined to a single muscular belly (semitendinosus, biceps, and splenius capitis muscles). Complete excision of the affected muscle was performed in all cases. One dog showed moderate lameness in the immediate postoperative period, resulting from the dorsal lifting of the scapula due to serratus ventralis tenotomy performed to remove the caudal insertion of the splenius capitis muscle. All the dogs recovered fully within one month, experiencing good clinical function. Histopathology showed complete tumour removal with no neoplastic fascial disruption in all cases. Compartmental excision provides effective local tumour control, representing an alternative to limb amputation or more radical excision if adjuvant radiotherapy is not an option for owners.

13.
Cancers (Basel) ; 14(24)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36551672

RESUMO

Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA. In our study, we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. A total of 41 AGASACAs with complete clinical and follow-up information were then analyzed by immunohistochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor-infiltrating lymphocytes (CD3 and CD20), which were evaluated within the tumor bulk (intratumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. The intratumor lymphocytes were predominantly CD3+ T-cells and were positively correlated with the number of PD-1+ intratumor lymphocytes (ρ = 0.36; p = 0.02). The peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with variable PD-1 expression (range 0-50%). PD-L1 expression negatively affected survival only in the subgroup of dogs treated with surgery alone (n = 14; 576 vs. 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets.

14.
Vet Sci ; 9(12)2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36548850

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) in dogs is uncommon and often associated with a good prognosis, although some cases prove to be aggressive. In human oncology HCC is often very aggressive and diagnostic methods and prognostic factors are widely used to predict its biological behaviour. These include the expression of PIVKA-II. METHODS: in order to identify a prognostic factor for canine HCC, we applied different methods of histological grading and investigated PIVKA-II expression in 22 HCC of dogs treated surgically and followed clinically for at least 2 years. RESULTS: Nineteen patients analysed have passed the observation period without tumour recurrence, while 3 died following the development of metastases. PIVKA-II was positive in 15/22 cases without correlation with prognosis or tumoural grading even if a trend of PIVKA-II negativity in low WHO grades as well as increased number of PIVKA-II positive cases in higher WHO grades weres observed. CONCLUSIONS: This work showed that, PIVKA-II cannot be considered either as a marker of malignancy or as a prognostic marker for canine HCC. The poor prognosis depends usually on the clinical presentation. Thus prognostic parameters in canine HCC able to predict its aggressive behaviour through histological examination are still missing. The most promising method, limited to our study, seems to be the WHO histological grading.

15.
Life (Basel) ; 12(12)2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36556464

RESUMO

Osteosarcoma (OSA) is the most common pediatric malignant bone tumor. Although surgery together with neoadjuvant/adjuvant chemotherapy has improved survival for localized OSA, most patients develop recurrent/metastatic disease with a dismally poor outcome. Therapeutic options have not improved for these OSA patients in recent decades. As OSA is a rare and "orphan" tumor, with no distinct targetable driver antigens, the development of new efficient therapies is still an unmet and challenging clinical need. Appropriate animal models are therefore critical for advancement in the field. Despite the undoubted relevance of pre-clinical mouse models in cancer research, they present some intrinsic limitations that may be responsible for the low translational success of novel therapies from the pre-clinical setting to the clinic. From this context emerges the concept of comparative oncology, which has spurred the study of pet dogs as a uniquely valuable model of spontaneous OSA that develops in an immune-competent system with high biological and clinical similarities to corresponding human tumors, including in its metastatic behavior and resistance to conventional therapies. For these reasons, the translational power of studies conducted on OSA-bearing dogs has seen increasing recognition. The most recent and relevant veterinary investigations of novel combinatorial approaches, with a focus on immune-based strategies, that can most likely benefit both canine and human OSA patients have been summarized in this commentary.

16.
Vet Comp Oncol ; 20(4): 890-900, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36054794

RESUMO

Osteosarcoma is the most common primary malignant bone tumour in dogs, characterized by a locally aggressive and highly metastatic behaviour. Despite the current standards of care, most dogs succumb to the disease, indicating the need for novel treatment strategies. Polo-like kinase 1 (PLK1) is dysregulated in a variety of human cancer types, including osteosarcoma, and induces c-Myc accumulation. The crosstalk between the two molecules coordinates cell proliferation, differentiation, self-renewal and apoptosis. Therefore, PLK1 has recently emerged as a potential therapeutic target, mainly in tumours overexpressing c-Myc. BI 2536 is a selective PLK1 inhibitor promoting mitotic arrest and apoptosis in a variety of cancer cells. This research aimed at evaluating PLK1 and c-Myc protein expression in 53 appendicular canine osteosarcoma (cOSA) samples and the in vitro effects of BI 2536 on a c-Myc and PLK1-overexpressing cOSA cell line (D17). PLK1 and c-Myc expression in cOSA samples showed no correlation with clinicopathological data. However, c-Myc overexpression was associated with a significantly reduced overall survival (p = .003). Western Blot and RT-qPCR assays revealed that D17 expressed high protein and transcript levels of both PLK1 and MYC. When treated with BI 2536 (range 2.5-15 nM) for 24 h, D17 showed a substantial decrease in cell growth, inducing apoptosis and G2 /M cell cycle arrest. Interestingly, under BI 2536 treatment, D17 showed decreased c-Myc protein levels. Consistent with human OSA, these preliminary data outline the prognostic value of c-Myc expression in cOSA and highlight the potential role of PLK1 as an antiproliferative therapeutic target for tumours overexpressing c-Myc.


Assuntos
Neoplasias Ósseas , Doenças do Cão , Osteossarcoma , Cães , Animais , Humanos , Linhagem Celular Tumoral , Doenças do Cão/tratamento farmacológico , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Osteossarcoma/genética , Osteossarcoma/veterinária , Osteossarcoma/tratamento farmacológico , Proliferação de Células , Apoptose , Neoplasias Ósseas/genética , Neoplasias Ósseas/veterinária , Neoplasias Ósseas/tratamento farmacológico , Quinase 1 Polo-Like
17.
J Immunother Cancer ; 10(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35580930

RESUMO

BACKGROUND: Melanoma is the most lethal form of skin cancer in humans. Conventional therapies have limited efficacy, and overall response is still unsatisfactory considering that immune checkpoint inhibitors induce lasting clinical responses only in a low percentage of patients. This has prompted us to develop a vaccination strategy employing the tumor antigen chondroitin sulfate proteoglycan (CSPG)4 as a target. METHODS: To overcome the host's unresponsiveness to the self-antigen CSPG4, we have taken advantage of the conservation of CSPG4 sequence through phylogenetic evolution, so we have used a vaccine, based on a chimeric DNA molecule encompassing both human (Hu) and dog (Do) portions of CSPG4 (HuDo-CSPG4). We have tested its safety and immunogenicity (primary objectives), along with its therapeutic efficacy (secondary outcome), in a prospective, non-randomized, veterinary clinical trial enrolling 80 client-owned dogs with surgically resected, CSPG4-positive, stage II-IV oral melanoma. RESULTS: Vaccinated dogs developed anti-Do-CSPG4 and Hu-CSPG4 immune response. Interestingly, the antibody titer in vaccinated dogs was significantly associated with the overall survival. Our data suggest that there may be a contribution of the HuDo-CSPG4 vaccination to the improvement of survival of vaccinated dogs as compared with controls treated with conventional therapies alone. CONCLUSIONS: HuDo-CSPG4 adjuvant vaccination was safe and immunogenic in dogs with oral melanoma, with potential beneficial effects on the course of the disease. Thanks to the power of naturally occurring canine tumors as predictive models for cancer immunotherapy response, these data may represent a basis for the translation of this approach to the treatment of human patients with CSPG4-positive melanoma subtypes.


Assuntos
Vacinas Anticâncer , Proteoglicanas de Sulfatos de Condroitina , Doenças do Cão , Melanoma , Proteínas de Membrana , Neoplasias Bucais , Animais , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Proteoglicanas de Sulfatos de Condroitina/imunologia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/imunologia , Cães , Melanoma/tratamento farmacológico , Melanoma/veterinária , Proteínas de Membrana/imunologia , Mimetismo Molecular/imunologia , Neoplasias Bucais/terapia , Neoplasias Bucais/veterinária , Filogenia , Estudos Prospectivos , Melanoma Maligno Cutâneo
18.
Vet Med Sci ; 8(2): 425-430, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35142089

RESUMO

BACKGROUND: An aneurysmal bone cyst (ABC) is a rare benign lytic lesion affecting the medullary canal of long bones. It has been widely reported in human medicine, but rarely described in domestic animals. OBJECTIVE: To report the surgical treatment and long term follow-up of a dog affected by ABC. METHODS: An 8-month-old, intact female Weimaraner was presented with lameness affecting the left front limb and progressive swelling of the mid-distal radius. Survey radiographs revealed a mid-distal diaphyseal radial lesion. Fine needle aspirates, biopsy, CT scan and histopathology results supported the diagnosis of ABC. Treatment consisted of partial corticotomy of the affected radius, filling of the cystic cavity with demineralised bone matrix and autologous bone graft and stabilisation using lag screws and a neutralisation plate. RESULTS: The long-term follow-up, at 36 post-operative months, showed no recurrence of the cyst and bone modelling. Comparing preoperative radiographs with those at 36 months, bone modelling reduced the radial area by 23.3% in the craniocaudal radiographic view and 30% in the mediolateral projection. CONCLUSIONS: This treatment was sucessful in the case here described, with a 3 years follow-up.


Assuntos
Cistos Ósseos Aneurismáticos , Doenças do Cão , Animais , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Cistos Ósseos Aneurismáticos/veterinária , Transplante Ósseo/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Feminino , Tomografia Computadorizada por Raios X
19.
Vet Surg ; 51(3): 397-408, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997760

RESUMO

OBJECTIVE: To report complications and long-term outcomes after submucosal resections of benign and malignant epithelial rectal masses. STUDY DESIGN: Retrospective multicentric study. SAMPLE POPULATION: Medical records of 93 dogs at 7 referral hospitals. METHODS: Records were reviewed for surgical time, diagnosis, margins, complications, and recurrences. Survival of dogs was evaluated based on tumor types, categorized as benign, carcinoma in situ, and carcinoma. The Kaplan-Meier survival curve and Cox proportional hazards analysis were used to determine the association of a range of variables with recurrence and survival time. RESULTS: Duration of follow up was 708 days (range, 25-4383). Twenty-seven dogs (29%) developed complications. Recurrence was identified in 20/93 (21%), with 12/20 recurrent masses treated with repeat submucosal resection. Median survival was not reached in any group. The 1-,2-, 5-year survival rates for carcinomas were 95%, 89%, and 73% respectively. However, overall survival was longer for benign tumors than carcinomas (P = .001). Recurrence was more likely when complications (P = .032) or incomplete margins (P = .023) were present. Recurrence was associated with an increased risk of death (P = .046). CONCLUSION: Submucosal resection of both benign and malignant rectal masses was associated with a low rate of severe complications and prolonged survival in the 93 dogs described here. CLINICAL SIGNIFICANCE: Submucosal resection is a suitable technique for resection of selected rectal masses.


Assuntos
Carcinoma , Doenças do Cão , Recidiva Local de Neoplasia , Neoplasias Retais , Animais , Carcinoma/cirurgia , Carcinoma/veterinária , Doenças do Cão/cirurgia , Cães , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/veterinária , Neoplasias Retais/cirurgia , Neoplasias Retais/veterinária , Reto/patologia , Estudos Retrospectivos , Resultado do Tratamento
20.
Vet Comp Oncol ; 20(1): 172-178, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34351034

RESUMO

The aim of the present study was to retrospectively assess whether spaying at the same time of mastectomy increased disease-free survival (DFS) in bitches with mammary tumours and to investigate the utility of clinical data when designing a surgical plan that includes gonadectomy. Characteristics of 225 bitches carrying 489 tumours were retrieved. Of the116 bitches that underwent surgery, 52 bitches underwent mastectomy and ovariectomy, 46 bitches underwent mastectomy alone, whereas 18 bitches were already spayed. Analysis by Kaplan-Meier and in-between groups comparisons using Student's T, Chi-square, and one-way ANOVA tests were performed. DFS was longer for bitches that underwent ovariectomy and mastectomy compared to those that were left intact (p = .00064) or were already spayed (p = .0098). Spaying status affected tumour size (spayed: 2.75 cm ± 2.72; intact: 1.76 cm ± 2.04; p = .039), but not malignancy (p > .05). Differences in age were detected between animals with benign and malignant tumours (years: 9.1 ± 2.8 and 10 ± 2.3; p = .004), with multiple and single tumours (years: 10.18 ± 2.6 and 9.3 ± 2.8; p = .007), and between purebred and mixed breed bitches (years: 10.46 ±1.78 and 9.27 ±2.68; p = .005). Malignant tumours were larger than benign ones (2.17 cm±2.31 and 1.34 cm ±1.82; p = .005) and size increased according to the degree of malignancy. DFS was shorter for animals presenting tumours >2 cm in size (p < .006) and with tumours in the first pair of thoracic mammary glands (p = .00009). Gonadectomy should be suggested to owners of intact bitches carrying mammary tumours and age, size of the tumour, and location should be carefully considered when performing surgery.


Assuntos
Doenças do Cão , Neoplasias Mamárias Animais , Animais , Doenças do Cão/cirurgia , Cães , Feminino , Neoplasias Mamárias Animais/patologia , Neoplasias Mamárias Animais/cirurgia , Mastectomia/veterinária , Estudos Retrospectivos , Análise de Sobrevida
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