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Project-core: | ||
description: Describes the core details of the project like project ID, summary, | ||
overall design, publication related details and any other supplementary links | ||
associated with the project | ||
properties: | ||
properties: | ||
project_id: | ||
description: Primary key or unique identified for a project | ||
type: string | ||
pattern: "^DO-[0-9]{4}$" | ||
example: "P034" | ||
summary: | ||
description: Summary of the experiment from which the project has been derived | ||
type: string | ||
example: "The identification of novel therapeutic strategies to overcome | ||
the intrinsic or acquired resistance to trametinib in mutant KRAS lung | ||
adenocarcinoma (LUAD) is a major challenge. This study analyzes the effects | ||
of trametinib in Id1, a key factor involved in the oncogenic KRAS pathway, | ||
and investigates the Id1 role in acquire resistance and synergy with immunotherapy | ||
in KRAS-driven LUAD. Restoring the antitumor immune response by blocking | ||
programmed-cell death protein 1 (PD-1) and programmed-cell death-ligand | ||
1 (PD-L1) pathway represents a major breakthrough in non-small-cell lung | ||
cancer (NSCLC) treatment. Nevertheless, a high proportion of LUAD patients | ||
with KRAS alterations remain refractory to this therapy. Material and | ||
Methods: To explore whether MEK1/2 inhibition reduces Id1 expression, | ||
in vitro and in vivo experiments were conducted in KRAS-mutant NSCLC cells | ||
and murine models. RNAseq analysis was performed to elucidate the pathways | ||
involved in Id1 inhibition. Apoptosis and PD-L1 expression was measured | ||
by flow cytometry. Synergy of trametinib combined with anti-PD1 was investigated | ||
in KRAS-mutant LUAD mouse models. Results: Using preclinical syngeneic | ||
KRAS-mutant lung cancer mouse models, we demonstrate that trametinib synergizes | ||
with PD-1 blockade to reduce lung cancer progression and increase mice | ||
overall survival. This antitumor activity was linked to the degradation | ||
of Id1 via proteasome, and an enhanced INF-Y-mediated PD-L1 tumor cell | ||
expression in KRAS-mutant tumor cells. This effect required CD8+ T cells, | ||
boosted the intratumoral CD8+/Treg ratio, reducing the intratumoral Treg/CD4+ | ||
ratio. Conclusions: Our data may support the role of Id1 in the trametinib | ||
antitumoral effect, sustaining the mitogen-activated protein kinases (MAPK) | ||
signaling pathway involved in the trametinib acquired resistance cells | ||
and sensitizing KRAS-mutant lung tumors to PD-1 inhibitors, through PD-L1 | ||
overexpression." | ||
overall_design: | ||
description: Overall design of the experiment as given by the author | ||
type: string | ||
example: "In order to investigate the molecular mechanisms involved in the | ||
trametinib-mediated Id1 downregulation, a global transcriptomic profiling | ||
using RNA sequencing analysis was performed on murine CMT167 and KLA lung | ||
cancer cells treated or not with trametinib" | ||
donor_derived_dataset: | ||
description: Whether the dataset has been derived from a donor or not | ||
type: boolean | ||
enum: | ||
- True | ||
- False | ||
- NA | ||
ontology_link: | ||
type: string | ||
description: Link to the ontology file | ||
url: https://bioportal.bioontology.org/ontologies/HRAVS?p=classes&conceptid=https%3A%2F%2Fpurl.humanatlas.io%2Fvocab%2Fhravs%23HRAVS_1002101 | ||
organism: | ||
description: The organism from which the samples were derived | ||
type: string | ||
example: "Homo sapiens" | ||
ontology_link: | ||
type: string | ||
description: Link to the ontology file | ||
url: https://bioportal.bioontology.org/ontologies/ORTH?p=classes&conceptid=http%3A%2F%2Fpurl.org%2Fnet%2Forth%23Organism | ||
cell_line: | ||
description: Identifier of the cell lines from which the samples were derived for this experiment | ||
There was a problem hiding this comment. Choose a reason for hiding this commentThe reason will be displayed to describe this comment to others. Learn more. @esheetah The description here should simply be the answer to "What is a cell-line"? Description is not a metadata field for the physical data model. It is simply to add more information about the attributes as a part of the conceptual model definition. There was a problem hiding this comment. Choose a reason for hiding this commentThe reason will be displayed to describe this comment to others. Learn more. Example section will cover what kind of values can be stored along with the above definition which fits better in the example section. |
||
type: string | ||
pattern: "^CVCL_[0-9]{4}$" | ||
example: "CVCL_0030" | ||
ontology_link: | ||
type: string | ||
description: Link to the ontology file | ||
url: https://www.cellosaurus.org/index.html | ||
author_cell_type: | ||
description: Cell types as curated from the publication/source for this experiment | ||
type: string | ||
example: "CMT167 cell" | ||
ontology_link: | ||
type: string | ||
description: Link to the ontology file | ||
url: https://bioportal.bioontology.org/ontologies/CCF?p=classes&conceptid=http%3A%2F%2Fpurl.org%2Fccf%2FCellType | ||
source_link: | ||
description: Link to source from where the data was fetched given as a url | ||
type: string | ||
format: alphanumeric | ||
example: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE236258 | ||
supplementary_links: | ||
description: External link(s) pointing to code, supplementary data files, | ||
or analysis files associated with the project which will not be uploaded | ||
type: array | ||
format: alphanumeric | ||
example: https://github.com/czbiohub/tabula-muris, http://celltag.org/ | ||
type: object | ||
version: 1.0.0 |
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@esheetah typo - identifier*
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Correcting this