Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study

Background: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. Methods: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. Results: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n¼5), breast(n¼8), other skin sites (n¼3), and soft tissue (n¼3). Target lesions (n¼54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). Conclusions: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas

Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis.

The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC

Association of body shape with amount of Arabian genetic contribution in the Lipizzan horse

Crossbreeding between individuals of different breeds and introgression, the transfer of genes between breeds and/or populations mediated primarily by backcrossing, have been characteristic tools used in the refinement or optimisation of practical horse breeding. In this study we analysed the genetic contribution of the Arabian horse to the gene pool of the Lipizzan horse and its association with the overall type via shape regression analysis in 158 Lipizzan horses from the Austrian federal stud farm of Piber and the Spanish Riding School. Although crossbreeding with Arabian horses took place between 1776 and 1945, we found a significant association between Lipizzan body shape (p &lt; 0.003) and individual coefficients of Arabian gene proportion, which varied from 21 to 29 %. In order to compare and interpret the estimated Lipizzan shape transitions from Iberian type towards the oriental type, we included a sample of 32 Shagya Arabians from the Slovak National stud farm Topol'ćianky. The estimated shape transitions in Lipizzans due to an increasing proportion of Arabian genes are similar to those we observed in the population comparison study of Lipizzan and Shagya Arabian horses. The main morphometric differences due to increasing Arabian genetic contributions in Lipizzans were found in the conformation of head, neck, withers, and legs. Although selection in the Austrian Lipizzan breed favours the Iberian type, Arabian shape characteristics are still present, indicating the segregation of Arabian founder haplotypes in the population. We also demonstrated that techniques of shape analysis are able to differentiate phenotypes associated with the gene pool and can be applied for phenotypic evaluation and prediction in crossbreeding programs

Known loci in the KIT and TYR genes do not explain the depigmented white coat colour of Austro-Hungarian Baroque donkey

The Italian Asinara donkey and the White Austro-Hungarian Baroque donkey share an identical coat colour phenotype which is characterised by unpigmented skin, white hair, white hooves and blue eyes. Whereas for the Asinara donkey the white coat colour phenotype was assigned to a recessive inherited missense mutation in the Tyrosinase gene (TYR), the underlying genetic background in the White Austro-Hungarian Baroque donkey has not been studied yet. Historical documents derived by the presence of Austro-Hungarian prisoners in the Asinara Island during the First World War might suggest a possible common origin of the same coat colour phenotype in the two breeds. Genotyping of this mutation in the TYR gene and the loci in the KIT gene associated with Dominant White and White Spotting phenotype, revealed, that none of the mutated alleles segregated in the White Austro-Hungarian Baroque Donkey breed. Also sequencing analysis of the TYR gene did not result in the detection of further candidate variants. Therefore, the TYR gene can be excluded as a possible candidate gene for this specific coat colour in the White Austro-Hungarian Baroque donkey. This result excludes a common genetic origin of the white coat colour of the Asinara and White Austro-Hungarian Baroque donkeys that historical documents could have suggested.Highlights Historical information indicated that the white (albino) Asinara donkey breed and the White Austro-Hungarian Baroque donkey breed could be genetically related. The TYR mutation identified in Asinara donkeys and known polymorphic sites in the KIT gene associated with depigmented white coat colour in donkeys do not segregate in the White Austro-Hungarian Baroque Donkey. Due to different underlying genetic background of one identical phenotype in two populations, no common ancestors can be assumed between Asinara donkey and White Austro-Hungarian Baroque donkey throughout the last century

Novel insights into Sabino1 and splashed white coat color patterns in horses

Within the framework of genome-wide analyses using the novel Axiom((R)) genotyping array, we investigated the distribution of two previously described coat color patterns, namely sabino1 (SBI), associated with the KIT gene (KI16+1037A), and splashed white, associated with the PAX3 gene (ECA6:g.11429753C>T; PAX3(C70Y)), including a total of 899 horses originating from eight different breeds (Achal Theke, Purebred Arabian, Partbred Arabian, Anglo-Arabian, Shagya Arabian, Haflinger, Lipizzan and Noriker). Based on the data we collected we were able to demonstrate that, besides Quarter horses, the PAX3(C70Y) allele is also present in Noriker (seven out of 189) and Lipizzan (three out of 329) horses. The SB1 allele was present in three breeds (Haflinger, 14 out of 98; Noriker, four out of 189; Lipizzan one out of 329). Furthermore, we examined the phenotypes of SB1- and PAX3(C70Y)-carrier horses for their characteristic white spotting patterns. None of the SB1/sb1-carrier horses met the criteria defining the Sabino1 pattern according to current applied protocols. From 10 heterozygous PAX3(C70Y)-carrier horses, two had nearly a splashed white phenotype. The results of this large-scale experiment on the genetic association of white spotting patterns in horses underline the influence of gene interactions and population differences on complex traits such as Sabino1 and splashed white

Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis

The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging