Genomic and proteomic profiling for cancer diagnosis in dogs

Global gene expression, whereby tumours are classified according to similar gene expression patterns or ‘signatures’ regardless of cell morphology or tissue characteristics, is being increasingly used in both the human and veterinary fields to assist in cancer diagnosis and prognosis. Many studies on canine tumours have focussed on RNA expression using techniques such as microarrays or next generation sequencing. However, proteomic studies combining two-dimensional polyacrylamide gel electrophoresis or two-dimensional differential gel electrophoresis with mass spectrometry have also provided a wealth of data on gene expression in tumour tissues. In addition, proteomics has been instrumental in the search for tumour biomarkers in blood and other body fluids

Cancer immunology and canine malignant melanoma: a comparative review

Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current “gold standard” treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics

A metastatic secretory gastric plasmacytoma with aberrant CD3 expression in a dog

A 10-year-old crossbred dog was presented with a 6-week history of hematemesis, melena, anorexia, and lethargy. Clinical evaluation revealed a gastric mass with a regional lymphadenomegaly as well as a monoclonal gammopathy manifesting as hyperglobulinemia. Cytologic and histopathologic analyses were consistent with a round cell neoplasm; neoplastic cells showed nuclear immunoreactivity for MUM1 and diffuse cytoplasmic reactivity for CD3. Polymerase chain reactions performed on fixed and fresh tissue identified a clonal rearrangement with an IgH primer set. An extramedullary plasmacytoma (EMP) was confirmed by cellular morphology and molecular diagnostics. Following an objective response to chemotherapy, the dog was euthanized 8 months after diagnosis, and a postmortem examination confirmed the clinical findings. This is the first reported case of a monoclonal gammopathy secondary to a gastric EMP coupled with aberrant expression of CD3 in an aggressive plasmacytic tumor, and highlights the utility of molecular diagnostics for classifying atypical hemolymphoid neoplasms

Remédiation cognitive et thérapie occupationnelle dans le traitement ambulatoire du patient souffrant de schizophrénie

Dans cet article, les auteurs décrivent un programme de réhabilitation comportementale pour patients souffrant de schizophrénie. Le programme combine la réhabilitation occupationnelle à l’entraînement cognitif, s’attaquant ainsi à deux des déficiences marquantes de ce trouble chronique. En plus de cibler ces deux types de déficiences, les auteurs ont aussi examiné l’impact de l’une sur l’autre. En effet, des recherches suggéraient que les déficiences cognitives peuvent indiquer une limite à la réhabilitation psychosociale de ces patients. L’intention des auteurs était d’examiner si le fait de remédier spécifiquement à ces déficits cognitifs mènerait la réhabilitation occupationnelle à des résultats supérieurs. Après une description détaillée du programme, ils présentent des données à l’appui de l’efficacité de ce type d’approche, à la fois pour améliorer les fonctions cognitives et mener à de meilleurs résultats fonctionnels.In the present paper, we describe a behavioral rehabilitation program for patients with schizophrenia. The program combines vocational rehabilitation with cognitive training, thereby addressing two of the hallmark impairments of this chronic disorder. In addition to targeting these two types of impairments, we also wished to investigate the impact of one on the other. Specifically, previous research has suggested that cognitive impairments may serve as rate-limiters in the psychosocial rehabilitation of patients with schizophrenia. Our intent was to investigate whether specifically addressing and remediating these cognitive deficits would in turn lead to superior outcomes in vocational rehabilitation. Following a detailed description of our program, we offer initial support for the efficacy of this type of approach in both improving cognitive function as well as leading to better functional outcomes.En este artículo, los autores describen un programa de rehabilitación comportamental para los pacientes que sufren de esquizofrenia. El programa combina la rehabilitación ocupacional con el entrenamiento cognitivo, enfrentándose así a dos deficiencias que marcan este trastorno crónico. Además de enfocarse en estos dos tipos de deficiencias, los autores también examinan el impacto de una en la otra. De hecho, los estudios sugieren que las deficiencias cognitivas pueden indicar un límite en la rehabilitación psicosocial de estos pacientes. La intención de los autores fue examinar si el hecho de remediar específicamente estos déficits cognitivos lleva a la rehabilitación ocupacional a resultados superiores. Después de una descripción detallada del programa, presentan datos que apoyan la eficacia de este tipo de enfoque para mejorar las funciones cognitivas y, al mismo tiempo, conducir a mejores resultados funcionales.Neste artigo, os autores descrevem um programa de reabilitação comportamental para pacientes que sofrem de esquizofrenia. O programa associa a reabilitação ocupacional ao treinamento cognitivo, combatendo, assim, duas das deficiências marcantes deste transtorno crônico. Além de tratar destes dois tipos de deficiências, os autores examinaram também o impacto de uma sobre a outra. De fato, as pesquisas salientaram que as deficiências cognitivas podem indicar um limite na reabilitação psicossocial destes pacientes. A intenção dos autores era examinar se o fato de remediar especificamente estes déficits cognitivos levaria a reabilitação ocupacional a resultados superiores. Após uma descrição detalhada do programa, eles apresentam dados para apoiar a eficácia deste tipo de abordagem para melhorar as funções cognitivas e ao mesmo tempo levar a melhores resultados funcionais

What Can Quantitative Gait Analysis Tell Us about Dementia and Its Subtypes? A Structured Review

Distinguishing dementia subtypes can be difficult due to similarities in clinical presentation. There is increasing interest in discrete gait characteristics as markers to aid diagnostic algorithms in dementia. This structured review explores the differences in quantitative gait characteristics between dementia and healthy controls, and between four dementia subtypes under single-task conditions: Alzheimer’s disease (AD), dementia with Lewy bodies and Parkinson’s disease dementia, and vascular dementia. Twenty-six papers out of an initial 5,211 were reviewed and interpreted using a validated model of gait. Dementia was associated with gait characteristics grouped by slower pace, impaired rhythm, and increased variability compared to normal aging. Only four studies compared two or more dementia subtypes. People with AD are less impaired in pace, rhythm, and variability domains of gait compared to non-AD dementias. Results demonstrate the potential of gait as a clinical marker to discriminate between dementia subtypes. Larger studies using a more comprehensive battery of gait characteristics and better characterized dementia sub-types are required

Assessment of sex-specific effects in a genome-wide association study of rheumatoid arthritis

Rheumatoid arthritis (RA) is three times more common in females than in males, suggesting that sex may play a role in modifying genetic associations with disease. We have addressed this hypothesis by performing sex-differentiated and sex-interaction analyses of a genome-wide association study of RA in a North American population. Our results identify a number of novel associations that demonstrate strong evidence of association in both sexes combined, with no evidence of heterogeneity in risk between males and females. However, our analyses also highlight a number of associations with RA in males or females only. These signals may represent true sex-specific effects, or may reflect a lack of power to detect association in the smaller sample of males, and thus warrant further investigation

Optimisation and validation of a PCR for Antigen Receptor Rearrangement (PARR) assay to detect clonality in canine lymphoid malignancies

PCR for antigen receptor gene rearrangements (PARR) analysis is being increasingly used to assist diagnosis of canine lymphoma. In this study, PARR was carried out on consecutive samples received as part of routine diagnostic practice from 271 patients: 195 with lymphoid malignancies, 53 with reactive conditions and 23 with other neoplasms. Initially, published primer sets were used but later minor primer modifications were introduced and primers were rationalised to give a PARR panel that provides a good compromise between sensitivity and cost. Results were compared to diagnoses made by histology or cytology, coupled with immunophenotyping by flow cytometry or immunohistochemistry where possible. After exclusion of 11 poor quality samples, 230/260 (88%) gave a clear result with 162/163 (99%) of samples classified as clonal and 56/67 (84%) classified as polyclonal giving results concordant with the cytological/histological diagnosis. Among 30 samples with equivocal results, 21 had clonal peaks in a polyclonal background and nine showed little amplification. These were from patients with a range of neoplastic and non-neoplastic conditions emphasising the need to interpret such results carefully in concert with other diagnostic tests. The combination of primer sets used in this study resulted in a robust, highly specific and sensitive assay for detecting clonality

Fibulin-2 is required for basement membrane integrity of mammary epithelium

Fibulin-2 (FBLN2) is a secreted extracellular matrix glycoprotein which has been associated with tissue development and remodelling. In the mouse mammary gland, FBLN2 can be detected during ductal morphogenesis in cap cells and myoepithelial cells at puberty and early pregnancy, respectively. In an attempt to assign its function, we knocked down Fbln2 in the mouse mammary epithelial cell line EpH4. FBLN2 reduction led to an increase in the size of spheroidal structures when compared to scrambled control shRNA-transduced cells plated on Matrigel matrix. This phenotype was associated with a disruption of the collagen IV sheath around the epithelial spheroids and downregulation of integrin β1, suggesting a role for FBLN2 in stabilizing the basement membrane (BM). In contrast to mice, in normal adult human breast tissue, FBLN2 was detected in ductal stroma, and in the interlobular stroma, but was not detectable within the lobular regions. In tissue sections of 65 breast cancers FBLN2 staining was lost around malignant cells with retained staining in the neighbouring histologically normal tissue margins. These results are consistent with a role of FBLN2 in mammary epithelial BM stability, and that its down-regulation in breast cancer is associated with loss of the BM and early invasion