Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Boswellic acid formulations are not suitable for additive treatment of pediatric high-grade glioma

ABSTRACT: Introduction: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM). Among others, one of the most frequently used CAM are boswellic acids (BA). Methods: The therapeutic effectiveness of the three main BA, alpha-boswellic acid (α-BA), beta-boswellic acid (β-BA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA) was analyzed in a histone 3 (H3)-wildtype and a H3.3K27M-mutant pedHGG cell line, either alone or in combination with radiotherapy and/or temozolomide chemotherapy. Cell viability, stemness properties and apoptosis as well as mRNA sequencing and in ovo tumor growth was investigated upon BA treatment. Results: Whereas α-BA and β-BA exert only mild anti-tumor effects in H3WT and H3.3K27M-mutated pedHGG cells, AKBA treatment reduced cell viability and stemness potential especially in H3.3K27M-mutant pedHGG cells. In addition, slight anti-inflammatory effects were observed after AKBA treatment of H3.3K27M-mutant pedHGG cells. However, no effects on apoptosis and in ovo tumor growth were found. Of note, α-BA and β-BA treatment even resulted in tumor promoting effects in both pedHGG cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214897 | GEO | 2023/08/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Evading immune evasion via reprograming of the tumor microenvironment by radiotherapy and simultaneous targeting of TGF-β/PD-L1

Project description:Tumor immunogenicity enhanced by radiotherapy (RT), is often counterbalanced by immune evasive mechanisms and tissue remodeling effects via upregulation of transforming growth factor-β (TGF-β) and programmed cell death-ligand 1 (PD-L1). We report that bintrafusp alfa (BA), a bifunctional fusion protein that simultaneously inhibits TGF-β and PD-L1, is a favorable combination partner for RT in eradicating multiple treatment-resistant tumor models. Beneficial effects of BA+RT (BART) are partly attributed to counterbalancing undesired RT effects and local tumor microenvironment reprograming, leading to reconstitution of tumor immunity and regression of spontaneous lung metastases. Intriguingly, BA, but neither TGF-β trap nor anti–PD-L1 alone, attenuates late-stage RT-induced lung fibrosis. Single cell transcriptome show TGF-β expression is confined to PD-L1+ endothelium and M2/lipofibroblast-like cells. Hence, superior effects of BA could be attributed to its ability to trap TGF-β to relevant PD-L1+ compartments. Here, we provide rationales that BART resensitizes tumors and broadens the therapeutic window.

2021-08-16 | GSE182004 | GEO

Tracking transcriptional changes in a species-specific manner during experimental hepatoblastoma progression in vivo

Project description:Hepatoblastoma is a primitive liver cancer occurring mainly in infants with defined molecular alterations driving its progression, which is difficult to model in vivo. Here we present a new animal model for hepatoblastoma on the chick chorioallantoic membrane (CAM), which recapitulates relevant features of hepatoblastoma in patients. Expression of classic tumor-associated proteins such as β-catenin, EpCAM and CK19 was maintained in acini-like organized tumors on CAM, as was synthesis of AFP, a tumor marker used for monitoring patient response. RNA sequencing revealed an unexpected molecular evolution of hepatoblastoma cells on the CAM, with significant deregulation of more than 6000 genes including more than half of all HOX genes. Bioinformatic analysis could clearly distinguish between tumor cell-expressed genes and chick host genes, thereby shedding new light on the complex interactions taking place during experimental hepatoblastoma progression. Importantly, human tumor suppressive ribosomal genes were downregulated after implantation, whereas mitochondrial genes encoding for anti-apoptotic peptides were strongly induced in vivo. Meprin-1α expression was increased during evolution of CAM tumors and confirmed by immunohistochemistry. Cisplatin, a commonly used chemotherapeutic agent for hepatoblastoma, showed significant anti-tumoral effects in this model. Our results broaden the understanding of the molecular adaptation process of human cancer cells to the microenvironment and might help to elaborate novel therapeutic concepts for the treatment of this pediatric liver tumor.

2018-04-17 | GSE101413 | GEO

Analysis of DNA methylation profiles in colorectal cancer cells treated with boswellic acids

Project description:Genome wide DNA methylation profiling of colorectal cancer cell lines treated with acetyl-11-keto-β-boswellic acid (AKBA) or 5-aza-2’-deoxycytidine (DAC). The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the colorectal cancer cell line SW48. Samples included non-treated, AKBA-treated, and DAC-treated SW48 cells.

2012-12-01 | GSE32275 | GEO

Genome-wide map of H3K27me3 before and after AKBA treatment in HaCaT cells

Project description:The goal of this study was to compare the distribution of H3K4me3 before and after AKBA treatment to understand how small molecule AKBA affects the epigenetic state. To do this we performed ChIP-seq with an H3K27me3 antibody.

2018-03-22 | GSE112142 | GEO

Analysis of DNA methylation profiles in colorectal cancer cells treated with boswellic acids

2012-12-01 | E-GEOD-32275 | biostudies-arrayexpress

AKBA regulates mRNA expression of mouse epidermis.

Project description:The goal of this study was to determine the effects of AKBA on mRNA expression of mouse epidermis.

2018-03-24 | GSE112248 | GEO

H3.3K27M mutant proteins reprogram epigenome by sequestering the PRC2 complex to poised enhancers

Project description:Expression of histone H3.3K27M mutant proteins in diffuse intrinsic pontine glioma (DIPG) results in a global reduction of tri-methylation of H3K27 (H3K27me3), and paradoxically, H3K27me3 peaks remain at hundreds of genomic loci, a dichotomous change that lacks mechanistic insights. Here we show that the PRC2 complex is sequestered at poised enhancers, but not at active promoters with high levels of H3.3K27M proteins, thereby contributing to the global reduction of H3K27me3. Moreover, the levels of H3.3K27M proteins are low at the retained H3K27me3 peaks and consequently having minimal effects on the PRC2 activity at these loci. H3K27me3-mediated silencing at specific tumor suppressor genes, including Wilms Tumor 1, promotes proliferation of DIPG cells. These results support a model in which the PRC2 complex is redistributed to poised enhancers in H3.3K27M mutant cells and supports the proliferation of DIPG cells in part through silencing of tumor suppressor gene WT1.

2018-07-02 | GSE94834 | GEO

Characterization of tumor-infiltrating T cells by TCR-β repertoire analyses

Project description:Local administration of IFN-α-producing proliferating myeloid cells (IFN-α-iPSC-pMCs) inhibited the tumor growth not only at the treatment site but also at the distant site (left). T cell receptor (TCR)-β chain repertoire and complementarity determining region 3 (CDR3) gene sequence analyses of tumor-infiltrating lymphocytes (TILs) showed marked enrichment of T cells with identical TCR-β chains in bilateral tumor tissues.

2019-02-13 | GSE126278 | GEO

A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities

Project description:Pediatric high-grade gliomas (pHGG) are lethal, incurable brain tumors frequently driven by clonal mutations in histone genes. They often harbor a range of additional genetic alterations that correlate with different ages, anatomic locations, and tumor subtypes. We developed models representing 16 pHGG subtypes driven by different combinations of alterations targeted to specific brain regions. Tumors developed with varying latencies and cell lines derived from these models engrafted in syngeneic, immunocompetent mice with high penetrance. Targeted drug screening revealed unexpected selective vulnerabilities—H3.3G34R/PDGFRAC235Yto FGFR inhibition, H3.3K27M/PDGFRAWTto PDGFRA inhibition, and H3.3K27M/PDGFRAWTand H3.3K27M/PPM1DΔC/PIK3CAE545Kto combined inhibition of MEK and PIK3CA. Moreover, H3.3K27Mtumors with PIK3CA, NF1, and FGFR1 mutations were more invasive and harbored distinct additional phenotypes, such as exophytic spread, cranial nerve invasion, and spinal dissemination. Collectively, these models reveal that different partner alterations produce distinct effects on pHGG cellular composition, latency, invasiveness, and treatment sensitivity.

2023-09-12 | GSE242998 | GEO

Evading immune evasion via reprograming of the tumor microenvironment by radiotherapy and simultaneous targeting of TGF-β/PD-L1

Project description:Single cell transcriptome showed TGF-β expression is confined to PD-L1+ endothelium and M2 /lipofibroblast-like cells. Hence, superior effects of BA could be attributed to its ability to trap TGF-β to relevant PD-L1+ compartments. Mice were irradiated (photon) and one group of mice was treated with Bintrafusp. Lungs were subsequently dissociated and processed with the 10x genomics 3 prime v2 kit.

2021-08-10 | E-MTAB-10633 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data