Browsing by Author "Hughes K"

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    Development of a Nomogram to Predict the Outcome for Patients with Soft Tissue Sarcoma.
    (MDPI (Basel, Switzerland), 2023-03-29) Bray JP; Munday JS; Dobson J; Hayes A; Hughes K
    Soft tissue sarcomas (STSs) are common cutaneous or subcutaneous neoplasms in dogs. Most STSs are initially treated by surgical excision, and local recurrence may develop in almost 20% of patients. Currently, it is difficult to predict which STS will recur after excision, but this ability would greatly assist patient management. In recent years, the nomogram has emerged as a tool to allow oncologists to predict an outcome from a combination of risk factors. The aim of this study was to develop a nomogram for canine STSs and determine if the nomogram could predict patient outcomes better than individual tumour characteristics. The current study provides the first evidence in veterinary oncology to support a role for the nomogram to assist with predicting the outcome for patients after surgery for STSs. The nomogram developed in this study accurately predicted tumour-free survival in 25 patients but failed to predict recurrence in 1 patient. Overall, the sensitivity, specificity, positive predictive, and negative predictive values for the nomogram were 96%, 45%, 45%, and 96%, respectively (area under the curve: AUC = 0.84). This study suggests a nomogram could play an important role in helping to identify patients who could benefit from revision surgery or adjuvant therapy for an STS.
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    Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer.
    (Springer Nature Limited, 2020-06-16) Strakova A; Nicholls TJ; Baez-Ortega A; Ní Leathlobhair M; Sampson AT; Hughes K; Bolton IAG; Gori K; Wang J; Airikkala-Otter I; Allen JL; Allum KM; Arnold CL; Bansse-Issa L; Bhutia TN; Bisson JL; Blank K; Briceño C; Castillo Domracheva A; Corrigan AM; Cran HR; Crawford JT; Cutter SM; Davis E; de Castro KF; De Nardi AB; de Vos AP; Delgadillo Keenan L; Donelan EM; Espinoza Huerta AR; Faramade IA; Fazil M; Fotopoulou E; Fruean SN; Gallardo-Arrieta F; Glebova O; Gouletsou PG; Häfelin Manrique RF; Henriques JJGP; Horta RS; Ignatenko N; Kane Y; King C; Koenig D; Krupa A; Kruzeniski SJ; Lanza-Perea M; Lazyan M; Lopez Quintana AM; Losfelt T; Marino G; Martínez Castañeda S; Martínez-López MF; Masuruli BM; Meyer M; Migneco EJ; Nakanwagi B; Neal KB; Neunzig W; Nixon SJ; Ortega-Pacheco A; Pedraza-Ordoñez F; Peleteiro MC; Polak K; Pye RJ; Ramirez-Ante JC; Reece JF; Rojas Gutierrez J; Sadia H; Schmeling SK; Shamanova O; Sherlock AG; Steenland-Smit AE; Svitich A; Tapia Martínez LJ; Thoya Ngoka I; Torres CG; Tudor EM; van der Wel MG; Vițălaru BA; Vural SA; Walkinton O; Wehrle-Martinez AS; Widdowson SAE; Zvarich I; Chinnery PF; Falkenberg M; Gustafsson CM; Murchison EP
    Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.