Laurie Rund

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Richard Tabor Greene

PUT

Patricia A. Beddows

Northwestern University

Mária Tóth

Institute for Geological and Geochemical Research, Research Centre for Astronomy and Earth Sciences, Hungarian Academy of Sciences

Huilong Hou

University of Maryland, College Park

Ahmed A. Farghaly

Virginia Commonwealth University

Gobind Das

Istituto Italiano di Tecnologia / Italian Institute of Technology

Maarten Kleinhans

Utrecht University

Paul Koch

University of California, Santa Cruz

Theivasanthi Thirugnanasambandan

Kalasalingam University

Anilkumar G Garag

Chanakya University

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Use of embryonic stem cells in livestock improvement

Abstract 2148: Image-guided catheter-based ultrasound thermal ablation of intramuscular and retroperitoneal sarcomas in the transgenic Oncopig cancer model

Soft-tissue sarcomas (STS) are aggressive, often lethal mesenchymal tumors that represent roughly... more Soft-tissue sarcomas (STS) are aggressive, often lethal mesenchymal tumors that represent roughly 1% of adult cancers. The 5-year survival rate of STS has remained unchanged for decades at 50%, highlighting the need for more effective therapies. We are developing protocols and assessing the treatment efficacy of 3D spatially-registered real-time image-guided needle/catheter based ultrasound (CBUS) ablative thermal therapy in STS induced in the transgenic Oncopig cancer model (OCM). The transgenic Oncopig carries a Cre recombinase inducible transgene encoding KRASG12D and TP53R167H; both mutations commonly in human cancers. Cre recombinase induces expression of the transgenes and transformation of cells in culture and rapid and reproducible development of leiomyosarcomas when introduced into the muscle of oncopigs. The flexibility of the model allowed induction of sarcomas in two clinically relevant intramuscular (IM) sites in both the hind limb and retroperitoneal (RP) regions, to closely simulate human disease. We have previously shown that these Oncopig tumors present the same transcriptional hallmarks as human STS including altered TP53 signaling, Wnt signaling activation and evidence of epigenetic reprogramming. Initial acute studies revealed that the tumors could be successfully grown in the muscle reaching mean tumor volume of 19.76cm3 (RP, n= 8) and 25.12cm3 (IM, n=14) cm3 within two weeks following AdCre (5.0x108 to 1.0x109 PFU) injections. Tumors were then treated utilizing ultrasound image guidance combined with 3D EM tracking to place the applicator in the target region. Sectored tubular transducers were introduced through a small skin incision and used to precisely deliver thermal energy to the treatment region. Tumors were treated for 6-9 minutes at 7 watts acoustic power (10.2W/cm2). Thermocouples were inserted into the tumors monitored temperature throughout the treatment. Post-treatment analysis revealed that the mean induced lesion volume exceeded the actual tumor volume for both IM (43.41 cm3) and RP (22.87 cm3) tumors with mean peak temperatures reaching 64.56 ° C (IM) and 58.75 ° C (RP). The mean peak thermal dose (thermal equivalent minutes at 43 ° C - TEM43) accumulated for IM tumors was 3.70E+08, and 1.46E+06 for RP tumors. Histopathology analysis verified that treatment areas reached past tumor margins using single applicator configuration. This study clearly demonstrates that the Oncopig is a suitable model in size and clinically relevant tumor type for evaluation of ultrasound ablation instrumentation. In addition, these STS treatment protocols can reliably and accurately target and treat tumor volumes plus surrounding margins. Future work will include monitoring of treatment lesions for up to 3 months post ablation. Funded by NIH 5R21CA195433 Citation Format: Laurie A. Rund, Goutam Ghoshal, Emery Williams, Paul Neubauer, Lance Frith, R Tamas Heffter, Patrick Roady, Lawrence B. Schook, E Clif Burdette. Image-guided catheter-based ultrasound thermal ablation of intramuscular and retroperitoneal sarcomas in the transgenic Oncopig cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2148.

Data from: Distinguishing migration events of different timing for wild boar in the Balkans

Aim: We compared the power of different nuclear markers to investigate genetic structure of south... more Aim: We compared the power of different nuclear markers to investigate genetic structure of southern Balkan wild boar. We distinguished between historic events, such as isolation in different refugia during glacial periods, from recent demographic processes, such as naturally occurring expansions. Location: Southern Balkans/Greece. Methods: We sampled 555 wild boars from 20 different locations in southern Balkans/Greece. All individuals were analysed with 10 microsatellites and a subgroup of 91 with 49,508 single nucleotide polymorphisms (SNPs). Patterns of genetic structure and demographic processes were assessed with Bayesian clustering, linkage disequilibrium and past effective population size estimation analysis. Results: Both microsatellite and SNP data analyses detected genetic structure caused by historic events and support the existence of three groups in the studied area. A hybrid zone between two of the groups was also detected. We also showed that genome-wide SNP data analysis can identify recent events in bottlenecked populations. Main conclusions: We inferred the three groups diverged ~50,000–10,000 yr bp when populations contracted to different refugia. Our findings strengthened the evidence that the southern Balkan area was a glacial refugium including further local smaller refugia. Genome-wide genotyping inferred a recent population expansion that can mimic a ‘refugium within refugium’ scenario. It seems that microsatellite data tend to overestimate genetic structure when genetic drift happens in bottlenecked populations over a short distance. Therefore, genome-wide SNPs are more powerful at inferring phylogeography in natural populations, resolving inconsistencies from mitochondrial and microsatellite data sets

Hippocampal Changes Elicited by Metabolic and Inflammatory Stressors following Prenatal Maternal Infection

Genes, Dec 26, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more

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