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MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer

ABSTRACT: MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer

PROVIDER: PRJNA576147 | ENA |

REPOSITORIES: ENA

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MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Essen]

Project description:MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Essen]

| PRJNA576313 | ENA

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Verona]

Project description:MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Verona]

| PRJNA576312 | ENA

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [RNA-Seq]

Project description:MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [RNA-Seq]

| PRJNA575380 | ENA

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Essen]

Project description:The MAP Kinase pathway is the index oncogenic signaling towards which many compounds have been developed for the treatment of KRAS-driven cancers, including pancreatic ductal adenocarcinoma (PDA). How targeted MEK1/2 inhibition (MEKi) alters the tumor-microenvironment (TME) of PDA is poorly understood. Here, we showed that transcriptional signatures of MAP Kinase activation are enriched in aggressive human PDA subtype, while short term MEKi treatment in mouse PDA induced subtype switching. Moreover, MEKi induced depletion of tumor-infiltrating macrophages, while augmenting infiltration by neutrophils. Depletion of macrophages is observed early during in vivo treatment and is at least partially due to their higher sensitivity to MEKi. Since tumor-associated macrophages are consistently reported to interfere with gemcitabine uptake by PDA cells, we tested a sequential combination of MEKi and gemcitabine, which showed superior antitumor activity in vivo. These findings suggest that MEKi-induced TME remodeling might be exploited to increase therapeutic responses in PDA.

2023-12-31 | GSE138481 | GEO

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [Verona]

2023-12-31 | GSE138477 | GEO

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer [RNA-Seq]

2023-12-31 | GSE138306 | GEO

MAP Kinase inhibition depletes tumor-infiltrating macrophages in mouse pancreatic cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-12-31 | GSE138483 | GEO

Distinct Gene Expression Profiles in Adult Mouse Heart Following Targeted MAP Kinase Activation

Project description:Three major MAP kinase signaling cascades, ERK, p38 and JNK, play significant roles in the development of cardiac hypertrophy and heart failure in response to external stress and neural/hormonal stimuli. In order to study the specific function of each MAP kinase branch in adult heart, we have generated three transgenic mouse models with cardiac specific and temporally regulated expression of activated mutants of Ras, MKK3 and MKK7, which are selective upstream activators for ERK, p38 and JNK, respectively. Gene expression profiles in transgenic adult hearts were determined using cDNA microarrays at both early (4-7 days) and late (2-4 weeks) time points following transgene induction. From this study, we revealed common changes in gene expression among the three models, particularly involving extracellular matrix remodeling. However, distinct expression patterns characteristic for each pathway were also identified in cell signaling, growth and physiology. In addition, genes with dynamic expression differences between early vs. late stages illustrated primary vs. secondary changes upon MAP kinase activation in adult hearts. These results provide an overview to both short term and long term effects of MAP kinase activation in heart and support some common as well as unique roles for each MAP kinase cascade in the development of heart failure. Keywords: MAP Kinase induction comparison, time course

2005-11-01 | GSE3530 | GEO

Characterization of immune cells infiltrating pancreatic islets using scRNA-seq

Project description:T cells infiltrate pancreatic islets during the progression of type 1 diabetes (T1D) but their differentiation states have not been completely defined. We used unbiased single-cell RNA sequencing analyses to gain further insight into the phenotypic complexity of islet-infiltrating T cells in non-obese diabetic (NOD) mice.

2024-01-22 | GSE125455 | GEO

Expression Profiling of MAP Kinase-Mediated Meiotic Progression in C. elegans

Project description:A unique allele of MAP kinase, mpk-1(ga111), displays a reversible, temperature-sensitive, tissue-specific defect in progression through meiotic prophase I. We performed gene expression profiling on mpk-1(ga111) animals at multiple times after shift to permissive temperature to identify candidate downstream effectors of MPK-1 signaling in the germline. This analysis delineated a cohort of genes whose expression requires MPK-1 (MAP kinase) signaling in germ cells in the pachytene stage of meiosis I. We analyzed six timepoints after MAP kinase mpk-1(ga111) mutants were shifted to a temperature permissive for meiotic progression. Each timepoint was sampled in triplicate. Control (mpk-1+) animals were sampled in triplicate at the beginning and end of the time series. All samples were compared to a common reference sample made of a mixture of both control samples.

2010-07-01 | E-GEOD-5069 | biostudies-arrayexpress

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