0000000001120277

AUTHOR

Frauke Nitzki

showing 2 related works from this author

Antitumor Effects of a Combined 5-Aza-2′Deoxycytidine and Valproic Acid Treatment on Rhabdomyosarcoma and Medulloblastoma in Ptch Mutant Mice

2009

Abstract Patched (Ptch) heterozygous mice develop medulloblastoma (MB) and rhabdomyosarcoma (RMS) resembling the corresponding human tumors. We have previously shown that epigenetic silencing of the intact Ptch allele contributes to tumor formation in this model. Here, we investigated whether targeting of epigenetic silencing mechanisms could be useful in the treatment of Ptch-associated cancers. A reduction of endogenous DNA methyltransferase1 (Dnmt1) activity significantly reduced tumor incidence in heterozygous Ptch knockout mice. A combined treatment with the Dnmt inhibitor 5-aza-2′deoxycytidine (5-aza-dC) and the histone deacetlyase (HDAC) inhibitor valproic acid (VPA) efficiently prev…

DNA (Cytosine-5-)-Methyltransferase 1Patched ReceptorsPatchedCancer Researchmedicine.drug_classGene ExpressionDecitabineReceptors Cell SurfaceBiologyDecitabineHistone DeacetylasesHistonesMice03 medical and health sciences0302 clinical medicineAntineoplastic Combined Chemotherapy ProtocolsRhabdomyosarcomamedicineAnimalsDNA (Cytosine-5-)-MethyltransferasesGene SilencingMuscle SkeletalRhabdomyosarcoma030304 developmental biologyMedulloblastomaMice Inbred BALB C0303 health sciencesValproic AcidHistone deacetylase inhibitorCancerAcetylationDNA Methylationmedicine.disease3. Good healthHistone Deacetylase InhibitorsMice Inbred C57BLPatched-1 Receptorstomatognathic diseasesOncology030220 oncology & carcinogenesisAzacitidineCancer researchDNMT1Epigenetic therapyMedulloblastomamedicine.drugCancer Research
researchProduct

Time-point and dosage of gene inactivation determine the tumor spectrum in conditional Ptch knockouts

2009

Mutations in Patched (PTCH) have been associated with tumors characteristic both for children [medulloblastoma (MB) and rhabdomyosarcoma (RMS)] and for elderly [basal cell carcinoma (BCC)]. The determinants of the variability in tumor onset and histology are unknown. We investigated the effects of the time-point and dosage of Ptch inactivation on tumor spectrum using conditional Ptch-knockout mice. Ptch heterozygosity induced prenatally resulted in the formation of RMS, which was accompanied by the silencing of the remaining wild-type Ptch allele. In contrast, RMS was observed neither after mono- nor biallelic postnatal deletion of Ptch. Postnatal biallelic deletion of Ptch led to BCC preca…

PatchedPatched ReceptorsCancer ResearchPathologymedicine.medical_specialtyAgingSkin NeoplasmsGene DosageReceptors Cell SurfaceBiologymedicine.disease_causeGene dosageGastrointestinal epitheliumLoss of heterozygosity03 medical and health sciencesMice0302 clinical medicineRhabdomyosarcomamedicineAnimalsGene SilencingRhabdomyosarcomaMuscle SkeletalGerm-Line MutationPeritoneal Neoplasms030304 developmental biologyGastrointestinal NeoplasmsMedulloblastomaMice Knockout0303 health sciencesMutationMuscle NeoplasmsCystsGeneral MedicinePTCH1 Genemedicine.disease3. Good healthPatched-1 Receptorstomatognathic diseasesCarcinoma Basal Cell030220 oncology & carcinogenesisMutationCancer researchPrecancerous ConditionsCarcinogenesis
researchProduct