The canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage’s worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer’s evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

Clinical and magnetic resonance imaging (MRI) findings, histological appearances and surgical outcomes of 18 dogs and one cat with spinal tumors are presented. Medical records of the cases admitted for spinal disorders were reviewed, and cases of spinal tumors that were diagnosed by MRI and confirmed by histological examination were included in this study. T1 weighted, T2 weighted and contrast enhanced T1 weighted images were taken and interpreted to evaluate the spinal tumors. The tumors were diagnosed as: meningioma (n = 6), ependymoma (n = 1), nerve sheath tumor (n = 4), metastatic spinal tumor (n = 3), osteosarcoma (n = 2), osteoma (n = 1), rhabdomyosarcoma (n = 1), and nephroblastoma (n = 1). Thirteen cases underwent surgical operation and the remaining six cases were euthanized at the request of the owners. The neurological status of the surgical cases did not deteriorate, except for one dog that showed ependymoma in the early period after the operation. These results indicate the potential for surgical gross total tumor removal of vertebral tumors to provide better quality of life and surgical collection of histological specimens for definitive diagnosis. For effective case management, dedicated MRI examination is important to accurate evaluation of the spinal tumors, and surgical treatment is useful for extradural and intradural-extramedullary spinal tumors.

No abstract

Treatment with both PEG-IFNalpha2b and UDCA improved CCl4 induced rat liver fibrosis. Significantly higher effects were obtained using these agents in combination.

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.