0000000000015373

AUTHOR

Lubor Borsig

0000-0003-2263-9545

showing 2 related works from this author

IL-17A mediated endothelial breach promotes metastasis formation

2015

Abstract The role of the IL23/IL17A axis in tumor–immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a−/− mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression …

0301 basic medicineGenetically modified mouseCancer ResearchPathologymedicine.medical_specialtyLung NeoplasmsEndotheliumImmunologyMelanoma ExperimentalVascular permeability610 Medicine & healthBiology10263 Institute of Experimental ImmunologyCapillary Permeability03 medical and health sciencesCarcinoma Lewis LungCell Line TumormedicineCell AdhesionAnimals1306 Cancer ResearchCell adhesionMice Knockout2403 ImmunologyLungMelanomaInterleukin-17Transendothelial and Transepithelial MigrationEndothelial Cellsmedicine.diseaseMice Inbred C57BL030104 developmental biologymedicine.anatomical_structureCell culture570 Life sciences; biologyInterleukin 17Endothelium VascularNeoplasm Transplantation
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A dual role of caspase-8 in triggering and sensing proliferation-associated DNA damage, a key determinant of liver cancer development.

2017

Summary Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis. Proliferation-associated DNA damage is sensed by a complex comprising caspase-8, FADD, c-FLIP, and a kinase-dependent function of RIPK1. This platform requires a non-apop…

0301 basic medicineGenome instabilityMaleliver; Hepatocellular carcinoma; DNA damage response; replication stress; apoptosisCancer ResearchDNA RepairCarcinogenesisFas-Associated Death Domain ProteinApoptosisurologic and male genital diseasesDNA damage responseDna Damage Response ; Apoptosis ; Hepatocellular Carcinoma ; Liver ; Replication StressHistonesMice0302 clinical medicineRisk FactorsFADDPhosphorylationCellular SenescenceCaspase 8biologyLiver Neoplasmshepatocellular carcinomaLiver regeneration3. Good healthHistoneOncologyReceptors Tumor Necrosis Factor Type I030220 oncology & carcinogenesisReceptor-Interacting Protein Serine-Threonine KinasesFemalebiological phenomena cell phenomena and immunityCell agingCarcinoma HepatocellularDNA damageDNA repairreplication stressCaspase 8liverArticleGenomic Instability03 medical and health sciencesAnimalsHepatectomyHumansCrosses GeneticCell ProliferationJNK Mitogen-Activated Protein KinasesCell BiologyLiver Regeneration030104 developmental biologyImmunologyChronic Diseasebiology.proteinCancer researchHepatocytesMyeloid Cell Leukemia Sequence 1 ProteinDNA Damage
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