Gene expression profiling of canine osteosarcoma reveals genes associated with short and long survival times

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling of spontaneous tumors in the dog offers a unique translational opportunity to identify prognostic biomarkers and signaling pathways that are common to both canine and human. Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Canine OS are highly comparable with their human counterpart with respect to histology, high metastatic rate and poor long-term survival. This study investigates the prognostic gene profile among thirty-two primary canine OS using canine specific cDNA microarrays representing 20,313 genes to identify genes and cellular signaling pathways associated with survival. This, the first report of its kind in dogs with OS, also demonstrates the advantages of cross-species comparison with human OS.</p> <p>Results</p> <p>The 32 tumors were classified into two prognostic groups based on survival time (ST). They were defined as short survivors (dogs with poor prognosis: surviving fewer than 6 months) and long survivors (dogs with better prognosis: surviving 6 months or longer). Fifty-one transcripts were found to be differentially expressed, with common upregulation of these genes in the short survivors. The overexpressed genes in short survivors are associated with possible roles in proliferation, drug resistance or metastasis. Several deregulated pathways identified in the present study, including Wnt signaling, Integrin signaling and Chemokine/cytokine signaling are comparable to the pathway analysis conducted on human OS gene profiles, emphasizing the value of the dog as an excellent model for humans.</p> <p>Conclusion</p> <p>A molecular-based method for discrimination of outcome for short and long survivors is useful for future prognostic stratification at initial diagnosis, where genes and pathways associated with cell cycle/proliferation, drug resistance and metastasis could be potential targets for diagnosis and therapy. The similarities between human and canine OS makes the dog a suitable pre-clinical model for future 'novel' therapeutic approaches where the current research has provided new insights on prognostic genes, molecular pathways and mechanisms involved in OS pathogenesis and disease progression.</p

HALON-hysterectomy by transabdominal laparoscopy or natural orifice transluminal endoscopic surgery : a randomised controlled trial (study protocol)

Acknowledgments The authors acknowledge the NOTES Investigators' team for taking care of the study participants; and Amanda McPhail for language correction and editing of the manuscript.Peer reviewedPublisher PD

Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) adnexectomy for benign pathology compared with laparoscopic excision (NOTABLE) : A protocol for a randomised controlled trial

M1 - 018059 Acknowledgments We thank the vNOTES investigators’ team for taking care of the study participants. We also thank Amanda McPhail for language correction and editing of the manuscript.Peer reviewedPublisher PD

Діагностика банкрутства в системі антикризового управління

Розглянуто питання відповідності і значимості діагностики фінансового стану кожної стадії антикризового управління. Діагностику банкрутства визначено як ретроспективне, оперативне і перспективне дослідження господарської діяльності та процесу управління підприємством, направлене на виявлення параметрів кризового розвитку за допомогою реалізації комплексу дослідницьких процедур, виявлення слабких ланок і "вузьких місць".Рассмотрены вопросы соответствия и значимости диагностики каждой стадии антикризисного управления. Диагностика банкротства определена как ретроспективное, оперативное и перспективное исследование хозяйственной деятельности и процесса управления предприятием, направленное на выявление параметров кризисного развития с помощью реализации комплекса исследовательских процедур, выявления слабых зон и «узких мест».The article analyzes issues of adequacy and role of diagnostics in all stage of anti-crisis management. The diagnostics of bankruptcy is defined as a retrospective, operative and prospective study of enterprise’s economic activity and management process that is directed to identification of parameters of crisis development by using comprehensive researches and to finding weak spots and "bottlenecks"

Ordered arrays of gold nanoparticles crosslinked by dithioacetate linkers for molecular devices

The final performance of a molecular electronic device is determined by the chemical structure of the molecular wires used in its assembly. Molecular place-exchange was used to incorporate di-thioacetate terminated molecules into ordered arrays of dodecanethiol capped gold nanoparticles. X-Ray photoelectron spectroscopy confirmed successful molecular replacement. Room-temperature molecular conductance of a statistically large number of devices reveals that conductance is enhanced by up to two orders of magnitude for the di-thioacetate terminated molecules. Density functional theory transport calculations were performed on five different configurations of the di-thioacetate molecules between gold electrodes, and the calculated average conductance values are in good agreement with the experimentally-observed conductance trend. Our findings highlight important cooperative effects of bridging neighboring gold nanoparticles and choice of appropriate molecular wires when designing devices for efficient transport

Adnexectomy by vaginal Natural Orifice Transluminal Endoscopic Surgery versus laparoscopy : results of a first randomised controlled trial (NOTABLE trial)

Peer reviewedPostprin

Identification of anti-proliferative kinase inhibitors as potential therapeutic agents to treat canine osteosarcoma

Osteosarcoma is the most common primary bone tumour in dogs but various forms of therapy have not significantly improved clinical outcomes. As dysregulation of kinase activity is often present in tumours, kinases represent attractive molecular targets for cancer therapy. The purpose of this study was to identify novel compounds targeting kinases with the potential to induce cell death in a panel of canine osteosarcoma cell lines. The ability of 80 well-characterized kinase inhibitor compounds to inhibit the proliferation of four canine osteosarcoma cell lines was investigated in vitro. For those compounds with activity, the mechanism of action and capability to potentiate the activity of doxorubicin was further evaluated. The screening showed 22 different kinase inhibitors that induced significant anti-proliferative effects across the four canine osteosarcoma cell lines investigated. Four of these compounds (RO 31-8220, 5-iodotubercidin, BAY 11-7082 and an erbstatin analog) showed significant cell growth inhibitory effects across all cell lines in association with variable induction of apoptosis. RO 31-8220 and 5-iodotubercidin showed the highest ability to potentiate the effects of doxorubicin on cell viability. In conclusion, the present study identified several potent kinase inhibitors targeting the PKC, CK1, PKA, ErbB2, mTOR and NF-κB pathways, which may warrant further investigations for the treatment of osteosarcoma in dogs