In cancer gene therapy there are basic elements that need to be accomplished in order to produce an effective therapy. These are specifi c targeting of cancer cells, high expression of trans-genes and low toxicity.We have used the telomerase promoter which is shown to be active in 85-90% of canine cancers and combined this with a two-step amplifi cation mechanism. In this system the telomerase promoter drives the transcription of a transcriptional activator protein which in turn activates a strong minimal promoter to transcribe the trans-gene of interest. We have tested this system in cell culture using telomerase positive and negative cell lines and have shown the ability of this system to be very active in telomerase positive cells. We have also compared our system with the GAL4-VP16 system which is commonly used in gene therapy.Results: Our system shows a high level of specifi city and sensitivity and it is superior to the GAL4-VP16 system. Conclusion:We have developed a system with a unique potential to target cancer cells and express trans-genes at a high level and believe that this system will be able to improve gene therapy mechanisms. Prospect:We are working on developing a conditionally replicative adenovirus using CAV-1 making it capable of replicating and inducing lysis in telomerase positive cells. Simultaneously we are on using the TRAIL gene for cancer cell killing.
Background: Forty dogs presented for brachycephalic airway obstructive syndrome with laryngeal collapse not over 1st degree (saccule eversion) underwent glottis endoscopic and radiographic skull measurements before surgery. Fifteen Pugs, fifteen French and ten English Bulldogs were included. The goals were prospectively to compare three common brachycephalic breeds for anatomical differences regarding glottis and skull measurements, and to assess if any correlation between glottis and skull measurements was present. Linear measurements were used to obtain glottis and skull indices. Correlations between glottis and skull indices and glottic measurements were evaluated. Finally, glottis indices were compared among the three breeds. Results: No correlation was found for glottis and skull indices. The glottic index differed among the three breeds (smaller in Pugs and higher in English Bulldogs), ultimately representing a morphologic indicator of the different larynx shape in the three breeds (more rounded in English Bulldogs, more elliptical in Pugs and in-between in French Bulldogs). Conclusions: The lack of correlation between skull/glottic indices does not support skull morphology as predictor of glottic morphology. As Pugs had the lowest glottic index, it may be speculated that Pugs' original narrow glottic width may predispose to further progressive respiratory deterioration more easily than in the other two breeds.
Background Brachycephalic dogs have abnormal breathing patterns similar to those in humans with obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome is associated with dyslipidemia, hyperglycemia, and insulin resistance. Despite the fact that anatomic and functional alterations are well described in brachycephalic dogs, little is known about the consequences of upper airway obstruction on systemic inflammatory response and metabolic profile. Objectives To describe history, clinical presentation, and anatomic abnormalities; to evaluate systemic inflammatory response and metabolic profile; and to identify possible associations among clinical signs, anatomic abnormalities, inflammatory response, and metabolic profile in brachycephalic dogs with airway obstruction. Animals Thirty purebred brachycephalic dogs with brachycephalic airway obstructive syndrome (BAOS). Methods Prospective study. The following information was recorded and studied: respiratory and digestive signs, airway and digestive endoscopic anomalies, presence or absence of tracheal hypoplasia, histologic evaluation of gastrointestinal tract biopsy specimens, serum concentrations of C‐reactive protein (CRP), fructosamine, insulin, glucose, triglyceride, cholesterol, and plasma concentrations of lipoprotein classes. Results A high proportion of dogs (76.7%) had gastrointestinal signs. Esophageal deviation, atony of the cardia of the stomach, and distal esophagitis were the most common endoscopic anomalies detected. Twenty‐six (86.6%) dogs had different degrees of laryngeal collapse. Gastrointestinal histologic evaluation identified mostly chronic inflammation. Glucose, fructosamine, triglycerides, cholesterol, CRP, pre‐beta, beta lipoproteins, and chylomicrons were increased to a variable extent. Significant associations among clinical signs, anatomic abnormalities, CRP, and metabolic profile were not found. Conclusion and Clinical Importance Despite the presence of inflammation and some mild metabolic derangements, the clinicopathological variables evaluated did not offer valuable information in dogs with BAOS.
The aim of this paper is to define the endoscopic bronchial anatomy of the cat and to adapt these findings to the bronchoscopic nomenclature previously described for the dog by Amis and McKiernan (Amis TC, McKiernan BC (1986) Systematic identification of endobronchial anatomy during bronchoscopy in the dog. American Journal of Veterinary Research 47(12), 2649-2657). In this study, the normal endoscopic bronchial anatomy was identified based on analysis of 10 air-dried feline lungs, two euthanased and eight healthy anesthetized cats using either a rigid or a flexible endoscope. Endoscopic photographs were taken during the examinations in the anesthetized cats for a photographic atlas. Corrosion casts were made from the 10 air-dried lungs to confirm the anatomy identified by bronchoscopy. With the results of our findings a bronchoscopic map of the feline bronchial tree and a photographic bronchoscopic atlas of the healthy cat were made.
Background Interstitial lung disease is a heterogeneous group of conditions characterized by severe radiographic changes and clinicopathological findings. However, in the vast majority of cases, the cause remains unknown. Case description In the present study, we reported the clinical case of a 3 years old female Bull Terrier presented in October 2020 to the Advanced Diagnostic Imaging Department of the Turin Veterinary Teaching Hospital with a progressive pulmonary illness characterized by dyspnea, exercise intolerance, and a diffuse and severe pulmonary interstitial pattern at imaging investigations. Considering the clinical findings, the dog was included in a serological survey for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in companion animals, showing positive results. Due to the further clinical worsening, the owners opted for euthanasia. At necroscopy, dog showed severe and chronic bronchopneumonia compatible with a Canine Idiopathic Pulmonary Fibrosis and with serological features linked to a SARS-CoV-2 infection. Conclusions The comparison of these lesions with those reported in humans affected by Coronavirus Disease 2019 (COVID-19) supports the hypothesis that these findings may be attributable to the post-acute sequelae of SARS-CoV-2 infection in a dog with breed predisposition to Canine Idiopathic Pulmonary Fibrosis (CIPF), although direct evidence of SARS-CoV-2 by molecular or antigenic approaches remained unsolved.
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