Histiocytic sarcoma in miniature schnauzers: 30 cases.

OBJECTIVES: To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. MATERIALS AND METHODS: Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded. Progression-free survival and overall survival time were calculated. RESULTS: Thirty dogs were included. Twenty-four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy - with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. CLINICAL SIGNIFICANCE: Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short-lived because of the aggressive nature of the disease.

Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells.

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer great hope for in vitro modeling of Parkinson's disease (PD), as well as for designing cell-replacement therapies. To realize these opportunities, there is an urgent need to develop efficient protocols for the directed differentiation of hESC/iPSC into dopamine (DA) neurons with the specific characteristics of the cell population lost to PD, i.e., A9-subtype ventral midbrain DA neurons. Here we use lentiviral vectors to drive the expression of LMX1A, which encodes a transcription factor critical for ventral midbrain identity, specifically in neural progenitor cells. We show that clonal lines of hESC engineered to contain one or two copies of this lentiviral vector retain long-term self-renewing ability and pluripotent differentiation capacity. Greater than 60% of all neurons generated from LMX1A-engineered hESC were ventral midbrain DA neurons of the A9 subtype, compared with ∼10% in green fluorescent protein-engineered controls, as judged by specific marker expression and functional analyses. Moreover, DA neuron precursors differentiated from LMX1A-engineered hESC were able to survive and differentiate when grafted into the brain of adult mice. Finally, we provide evidence that LMX1A overexpression similarly increases the yield of DA neuron differentiation from human iPSC. Taken together, our data show that stable genetic engineering of hESC/iPSC with lentiviral vectors driving controlled expression of LMX1A is an efficient way to generate enriched populations of human A9-subtype ventral midbrain DA neurons, which should prove useful for modeling PD and may be helpful for designing future cell-replacement strategies.