Electrochemotherapy with cisplatin enhances local control after surgical ablation of fibrosarcoma in cats: an approach to improve the therapeutic index of highly toxic chemotherapy drugs

<p>Abstract</p> <p>Background</p> <p>Cancer is one of the most difficult current health challenges, being responsible for millions of deaths yearly. Systemic chemotherapy is the most common therapeutic approach, and the prevailing orientation calls for the administration of the maximum tolerated dose; however, considerable limitations exist including toxicities to healthy tissues and low achievable drug concentrations at tumor sites. Electrochemotherapy (ECT) is a tumor treatment that combines the systemic or local delivery of anticancer drugs with the application of permeabilizing electric pulses. In this article we evaluate the capability of ECT to allow the use of cisplatin despite its high toxicity in a spontaneous feline model of soft tissue sarcoma.</p> <p>Methods</p> <p>A cohort of sixty-four cats with incompletely excised sarcomas were treated with cisplatin-based adjuvant ECT and monitored for side effects. Their response was compared to that of fourteen cats treated with surgery alone.</p> <p>Results</p> <p>The toxicities were minimal and mostly treated symptomatically. ECT resulted in increased local control (median not reached at the time of writing) with a mean time to recurrence of 666 days versus 180 of controls.</p> <p>Conclusions</p> <p>We conclude that ECT is a safe and efficacious therapy for solid tumors; its use may be considered as part of strategies for the reintroduction of drugs with a narrow therapeutic index in the clinical protocols.</p

Origins of cattle on Chirikof Island, Alaska, elucidated from genome-wide SNP genotypes

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Modelling the Health Impact of an English Sugary Drinks Duty at National and Local Levels

Increasing evidence associates excess refined sugar intakes with obesity, Type 2 diabetes and heart disease. Worryingly, the estimated volume of sugary drinks purchased in the UK has more than doubled between 1975 and 2007, from 510ml to 1140ml per person per week. We aimed to estimate the potential impact of a duty on sugar sweetened beverages (SSBs) at a local level in England, hypothesising that a duty could reduce obesity and related diseases. Methods and Findings We modelled the potential impact of a 20% sugary drinks duty on local authorities in England between 2010 and 2030. We synthesised data obtained from the British National Diet and Nutrition Survey (NDNS), drinks manufacturers, Office for National Statistics, and from previous studies. This produced a modelled population of 41 million adults in 326 lower tier local authorities in England. This analysis suggests that a 20% SSB duty could result in approximately 2,400 fewer diabetes cases, 1,700 fewer stroke and coronary heart disease cases, 400 fewer cancer cases, and gain some 41,000 Quality Adjusted Life Years (QALYs) per year across England. The duty might have the biggest impact in urban areas with young populations. Conclusions This study adds to the growing body of evidence suggesting health benefits for a duty on sugary drinks. It might also usefully provide results at an area level to inform local price interventions in England

A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways.</p> <p>Methods</p> <p>We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p> <p>Results</p> <p>Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene <it>FANCM </it>(ORs 1.9-2.0, <it>P </it>= 0.003-0.004) and 2 SNPs downstream of the growth hormone gene <it>GH1 </it>(OR 1.6, <it>P </it>= 0.002; OR 0.5, <it>P </it>= 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: <it>MDM2</it>, <it>MPG</it>, <it>FGF2</it>, <it>FGFR3</it>, <it>GNRH2</it>, and <it>IGF1</it>.</p> <p>Conclusions</p> <p>Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings.</p

Computed Tomography-guided fine-needle aspiration and tissue-core biopsy of bone lesions in small animals

Nell'uomo, la biopsia TC-guidata a mano libera è un metodo accurato per ottenere dei campioni di tessuto. Ci sono pochi lavori di questa tecnica in medicina veterinaria. Nel presente studio, 21 cani e 2 gatti sono stati sottoposti a biopsia TC-guidata (17 animali) o ago aspirato fine TC-guidato (6 animali) di lesioni ossee. Due delle 17 biospie sono state anche sottoposta ad esame colturale. Tutte le 17 biospie erano diagnostiche (accuratezza 100%). Cinque dei sei aghi aspirati fini erano diagnostici (accuratezza 83.3%). L'accuratezza totale era 95.7%. In un aspirato, la qualità citologica è stata considerata insufficiente in quanto conteneva solo sangue. Non si sono evidenziate complicazioni maggiori. Sono state diagnosticate 14 lesioni neoplastiche, 2 infezioni, e 6 lesioni benigne. L'esame TC dopo somministrazione di mezzo di cotnrasto endovenoso ha aggiunto informazioni utili per evitare grossi vasi e per biopsare tessuto vitale. La bipsia e l'ago aspirato fine TC-guidati a mano libera sembra essere una tecnica sicura e molto accurata per la diagnosi di patologie ossee nei piccoli animaliIn humans, free-hand computed tomography (CT)-guided biopsy is an accurate method to obtain a tissue sample. There are only a few reports of this technique in veterinary medicine. In the present study, 21 dogs and two cats underwent a free-hand CT-guided tissue-core biopsy (17 animals) or fine-needle aspiration (six animals) of a bone lesion. Two out of 17 tissue-core samples were also cultured. All 17 tissue-core biopsy samples were diagnostic (accuracy of 100%). Five out of six aspirates were diagnostic (accuracy of 83.3%). The overall accuracy was 95.7%. In one aspirate, cytologic quality was insufficient containing only blood. No major complications were encountered. Fourteen neoplastic, two infectious and six benign lesions were diagnosed. CT examination after intravenous contrast medium added useful information to avoid large vessels and to biopsy-viable tissue. Free-hand CT-guided tissue-core biopsy and aspiration appears to be a safe and very accurate procedure for use in the diagnosis of bone-associated diseases in small animal