Dataset Information

Multi-organ Mapping of Cancer Risk.

ABSTRACT: Cancers are distributed unevenly across the body, but the importance of cell intrinsic factors such as stem cell function in determining organ cancer risk is unknown. Therefore, we used Cre-recombination of conditional lineage tracing, oncogene, and tumor suppressor alleles to define populations of stem and non-stem cells in mouse organs and test their life-long susceptibility to tumorigenesis. We show that tumor incidence is determined by the life-long generative capacity of mutated cells. This relationship held true in the presence of multiple genotypes and regardless of developmental stage, strongly supporting the notion that stem cells dictate organ cancer risk. Using the liver as a model system, we further show that damage-induced activation of stem cell function markedly increases cancer risk. Therefore, we propose that a combination of stem cell mutagenesis and extrinsic factors that enhance the proliferation of these cell populations, creates a "perfect storm" that ultimately determines organ cancer risk. VIDEO ABSTRACT.

SUBMITTER: Zhu L

PROVIDER: S-EPMC5067024 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multi-organ Mapping of Cancer Risk.

Zhu Liqin L Finkelstein David D Gao Culian C Shi Lei L Wang Yongdong Y López-Terrada Dolores D Wang Kasper K Utley Sarah S Pounds Stanley S Neale Geoffrey G Ellison David D Onar-Thomas Arzu A Gilbertson Richard James RJ

Cell 20160801 5

Cancers are distributed unevenly across the body, but the importance of cell intrinsic factors such as stem cell function in determining organ cancer risk is unknown. Therefore, we used Cre-recombination of conditional lineage tracing, oncogene, and tumor suppressor alleles to define populations of stem and non-stem cells in mouse organs and test their life-long susceptibility to tumorigenesis. We show that tumor incidence is determined by the life-long generative capacity of mutated cells. This ...[more]

PMID: 27565343

Similar Datasets

Project description:Background and objectiveImmune checkpoint inhibitor (ICI)-associated myocarditis is a fatal immune-related adverse events (irAEs), which is prone to affecting multiple organ systems. Multi-organ irAEs have not been fully studied in ICI-associated myocarditis. Therefore, we aimed to explore the impact of multi-organ irAEs on ICI myocarditis in terms of clinical features, treatment, and prognosis.MethodsThis was a retrospective study. The clinical data of ICI myocarditis patients were collected from 6 hospitals in China. The risk factors and characteristics of pure myocarditis and multi-organ irAEs were analyzed. The overall survival (OS) after myocarditis was analyzed and univariate and multivariate regression analysis were performed.ResultsA total of 46 patients were analyzed in this study. Multi-organ irAEs were common (30/46, 65.2%) and prone to severe heart failure. The severe myocarditis was observed in 32 patients (69.6%). When myocarditis occurred, neutrophil to lymphocyte ratio, C-reactive protein, lactate dehydrogenase, interleukin (IL)-6, IL-10, creatine kinase, MB isoenzyme of creatine kinase, and brain natriuretic peptide increased from baseline, but absolute lymphocyte count decreased. Thymoma (B2/B3) was a risk factor for multi-organ irAEs. Heart failure and myocarditis were more severe in patients with multi-organ irAEs and require early corticosteroid therapy (<24 hours). Univariate analysis showed that age ≥ 60 years, myocarditis (grade 3-4), heart failure (grade 3-4), multi-organ irAEs, and severe myocarditis were associated with OS after myocarditis. After adjusting for other factors, heart failure (grade 3-4) was an independent risk factor for immune-related myocarditis (HR: 6.655, 95% CI: 1.539-28.770, p=0.011).ConclusionPatients with ICI-associated myocarditis had multi-organ irAEs with a high incidence of severe myocarditis, mortality, and poor prognosis. Thymoma was prone to those patients with multiple organs involvement. Patients could benefit from early corticosteroid intervention. Heart failure (grade 3-4) was an independent risk factor for OS after myocarditis.

Dataset Information

Multi-organ Mapping of Cancer Risk.

Publications

Multi-organ Mapping of Cancer Risk.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets