Gene Expression Profiles of Sporadic Canine Hemangiosarcoma Are Uniquely Associated with Breed

The role an individual's genetic background plays on phenotype and biological behavior of sporadic tumors remains incompletely understood. We showed previously that lymphomas from Golden Retrievers harbor defined, recurrent chromosomal aberrations that occur less frequently in lymphomas from other dog breeds, suggesting spontaneous canine tumors provide suitable models to define how heritable traits influence cancer genotypes. Here, we report a complementary approach using gene expression profiling in a naturally occurring endothelial sarcoma of dogs (hemangiosarcoma). Naturally occurring hemangiosarcomas of Golden Retrievers clustered separately from those of non-Golden Retrievers, with contributions from transcription factors, survival factors, and from pro-inflammatory and angiogenic genes, and which were exclusively present in hemangiosarcoma and not in other tumors or normal cells (i.e., they were not due simply to variation in these genes among breeds). Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) was among genes preferentially enriched within known pathways derived from gene set enrichment analysis when characterizing tumors from Golden Retrievers versus other breeds. Heightened VEGFR1 expression in these tumors also was apparent at the protein level and targeted inhibition of VEGFR1 increased proliferation of hemangiosarcoma cells derived from tumors of Golden Retrievers, but not from other breeds. Our results suggest heritable factors mold gene expression phenotypes, and consequently biological behavior in sporadic, naturally occurring tumors

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Clinical, CT, and ultrasonographic features of canine and feline pleural and peritoneal carcinomatosis and sarcomatosis

Carcinomatosis and sarcomatosis describe the widespread dissemination of metastatic neoplastic cells throughout the body. Studies describing their clinical and imaging features in veterinary patients are limited. The objective of this retrospective, multicenter, cross-sectional study is to describe the clinical, ultrasonographic, and CT features of pleural and peritoneal carcinomatosis and sarcomatosis in dogs and cats to aid detection and differentiation of these lesions. Medical records and CT and ultrasonographic images were reviewed. Although a large degree of overlap was observed between the imaging features and clinical signs of canine and feline carcinomatosis and sarcomatosis, some distinguishing features were observed. Dogs were significantly more likely to present with abdominal pain compared to cats (P = .022), whereas cats more commonly presented with inappetence (P = .019). Dogs with sarcomatosis had a significantly heavier bodyweight than dogs with carcinomatosis (P = .005), largely due to a higher prevalence of splenic hemangiosarcoma in this patient cohort. Peritoneal effusion was more frequently observed in dogs with carcinomatosis compared to dogs with sarcomatosis (P = .021). Imaging and clinical features observed in this study may help to distinguish sarcomatosis and carcinomatosis lesions. Due to the large degree of overlap observed, cytological or histopathological analysis is recommended for definitive diagnosis