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: Osteosarcoma (OSA) is a highly metastatic pediatric bone tumor. Adjuvant chemotherapy and surgical resection represent standard treatments; however, the prognosis is still poor. Effective strategies are urgently needed. Chondroitin sulfate proteoglycan (CSPG)4 is a transmembrane proteoglycan with a low expression in normal tissues but high expression in several solid tumors, where it plays a central tumorigenic role. Therefore, it represents a promising therapeutic target. The high homology between human and canine CSPG4 and the recognized translational power of canine tumors as preclinical models for human malignancies prompted us to evaluate CSPG4 expression and the consequences of its immune-targeting for both human and canine OSA treatment. Methods: We analyzed CSPG4 overexpression in human and canine OSA samples and its significance for the survival of OSA patients. We exploited functional in vitro experiments to assess the antitumor potential of CSPG4 immune-targeting. Results: CSPG4 is overexpressed in OSA and has possible clinical implications as suggested by an evident correlation between CSPG4 overexpression and a shorter survival for both OSA-affected humans and dogs. The potential of CSPG4 immune-targeting for OSA treatment came from the ability of anti-CSPG4 monoclonal antibodies and sera, derived from human-CSPG4-DNA vaccinated canine patients, to significantly inhibit human and canine CSPG4-positive OSA cell proliferation, migration, and osteospheres generation. Moreover, CSPG4 immune-targeting has been shown to potentiate the effect of doxorubicin. Conclusions: Overall, these results provide the rationale to investigate the CSPG4 immune-targeting as a promising weapon for the treatment of CSPG4-positive OSA canine patients, to be successfully translated to a human setting.

A 12-year-old male cat was referred for progressive limb weakness lasting 2 weeks. Physical examination detected muscle atrophy and bilateral renomegaly with distortion of the renal contours. The cat was ambulatory but tetraparetic. It showed a peculiar posture on forelimbs with bilateral flexion of the carpi and extrarotation of forearms. The cat was unable to go upstairs or jump. Neurological examination showed findings compatible with peripheral nervous system involvement. Histopathological findings revealed a high grade non-B, non-T cell renal lymphoma and peripheral neuropathy characterised by demyelination, axonal degeneration and muscle denervation. In the absence of congenital, metabolic and infectious diseases or exposure to toxins, a paraneoplastic peripheral neuropathy was hypothesised. In humans and dogs, paraneoplastic peripheral neuropathies have been documented with different neoplastic processes including lymphoproliferative disorders. To the authors' knowledge, this is the first report of suspected paraneoplastic polyneuropathy in a cat with malignant tumour.

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Case summaryA 14-year-old, neutered male European shorthair cat was evaluated for a routine health check. The owner did not report any clinical signs except for respiratory stridor. On physical examination the main findings were broad facial features and increased interdental spaces. On haematology, a mild, non-regenerative anaemia was detected, whereas the serum biochemistry profile and urinalysis were unremarkable. The serum glucose concentration was within the reference interval. Serum insulin-like growth factor-1 concentration was markedly elevated (>1600 ng/ml). The basal serum growth hormone concentration was elevated and decreased only mildly after somatostatin administration. Basal serum insulin concentration was high, and the insulin concentration increased considerably after glucose loading, consistent with insulin resistance. CT scanning of the skull showed an enlarged pituitary gland and increased skull bone thickness. The final diagnosis was acromegaly.Relevance and novel informationThese findings demonstrate that acromegaly should be pursued and suspected in cats other than those with diabetes mellitus.