Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Modified C-type natriuretic peptide normalizes tumor vasculature and improves solid tumor therapies

ABSTRACT: Modified C-type natriuretic peptide normalizes tumor vasculature and improves solid tumor therapies

PROVIDER: PRJNA1016266 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR26048954.fastq.gz	Fastqsanger.gz
	SRR26048955.fastq.gz	Fastqsanger.gz
	SRR26048956.fastq.gz	Fastqsanger.gz
	SRR26048957.fastq.gz	Fastqsanger.gz
	SRR26048958.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 6

Similar Datasets

Modified C-type natriuretic peptide normalizes tumor vasculature and improves solid tumor therapies

Project description:Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic problems and generation of immunosuppressive TME undermine the efficacy of cancer treatment. These problems can be partially alleviated by angiogenesis inhibitors. Here we propose an alternative agonist-based normalization approach utilizing a derivative of the C-type natriuretic peptide (dCNP). This well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and reinvigorated the anti-tumor immune responses. Treatment with dCNP decelerated growth of primary tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio- or immune-therapeutic regimens increased their efficacy against solid tumors. These results demonstrate the proof of principle for using activators of normalized angiogenesis to improve therapies against solid tumors and characterize dCNP as the first in class amongst such agents.

2023-10-16 | GSE243040 | GEO

Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.

Project description:Deficit of oxygen and nutrients in the tumor microenvironment (TME) triggers abnormal angiogenesis that produces dysfunctional and leaky blood vessels, which fail to adequately perfuse tumor tissues. Resulting hypoxia, exacerbation of metabolic disturbances, and generation of an immunosuppressive TME undermine the efficacy of anticancer therapies. Use of carefully scheduled angiogenesis inhibitors has been suggested to overcome these problems and normalize the TME. Here, we propose an alternative agonist-based normalization approach using a derivative of the C-type natriuretic peptide (dCNP). Multiple gene expression signatures in tumor tissues were affected in mice treated with dCNP. In several mouse orthotopic and subcutaneous solid tumor models including colon and pancreatic adenocarcinomas, this well-tolerated agent stimulated formation of highly functional tumor blood vessels to reduce hypoxia. Administration of dCNP also inhibited stromagenesis and remodeling of the extracellular matrix and decreased tumor interstitial fluid pressure. In addition, treatment with dCNP reinvigorated the antitumor immune responses. Administration of dCNP decelerated growth of primary mouse tumors and suppressed their metastases. Moreover, inclusion of dCNP into the chemo-, radio-, or immune-therapeutic regimens increased their efficacy against solid tumors in immunocompetent mice. These results demonstrate the proof of principle for using vasculature normalizing agonists to improve therapies against solid tumors and characterize dCNP as the first in class among such agents.

| S-EPMC11866103 | biostudies-literature

Oncofetal reprogramming of the tumor vasculature

Project description:Oncofetal reprogramming of the tumor vasculature

| PRJNA1027431 | ENA

Depletion of ADAM12+ MSCs normalizes the tumor stromal microenvironment

Project description:Depletion of ADAM12+ MSCs normalizes the tumor stromal microenvironment

| PRJNA852197 | ENA

Endothelial cell-specific LAT1 ablation normalizes tumor vasculature.

Project description:Some endothelial cells in the tumor vasculature express a system L amino acid transporter, LAT1. To elucidate the role of LAT1 in tumor-related endothelial cells, tumor cells were injected into endothelial cell-specific LAT1 conditional knockout mice (Slc7a5flox/flox; Cdh5-Cre-ERT2), and we found that the shape of the tumor vasculature was normalized and the size and numbers of lung metastasis was reduced. TNF-α-induced expression of VCAM1 and E-selectin at the surface of HUVEC, both of which are responsible for enhanced monocyte attachment and premetastatic niche formation, was reduced in the presence of LAT1 inhibitor, nanvuranlat. Deprivation of tryptophan, a LAT1 substrate, mimicked LAT1 inhibition, which led to activation of MEK1/2-ERK1/2 pathway and subsequent cystathionine γ lyase (CTH) induction. Increased production of hydrogen sulfide (H2S) by CTH was at least partially responsible for tumor vascular normalization, leading to decreased leakiness and enhanced delivery of chemotherapeutic agents to the tumor.

| S-EPMC11457854 | biostudies-literature

Vaccination against oncofetal targets in the tumor vasculature

Project description:Vaccination against oncofetal targets in the tumor vasculature

| PRJNA1191492 | ENA

Effects of a vaccine against the tumor vasculature

Project description:Effects of a vaccine against the tumor vasculature

| PRJNA723195 | ENA

Heterogeneity of Breast Cancer Vasculature

Project description:Tumor-associated breast vasculature was laser-cappture microdissected from IDC breast cancer cases. The goal of the study was to characterize the heterogeneity of breast tumor-associated vasculature and identify gene expression signatures predictive of clinical outcome. common reference design, 32 samples

2010-09-19 | E-GEOD-15363 | biostudies-arrayexpress

Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug

Project description:Tumor vasculature are structurally chaotic and functionally inefficient. Restoring aberrant tumor blood vessels, or “normalize” the tumor vasculature can alleviate hypoxia and enhance intra-tumoral drug delivery. However, identifying tumor vascular normalizing drugs are currently hampered by an absence of efficient screening platform. We aimed to develop a robust method to visualize, digitalize and evaluate the structural and functional changes of tumor vasculature in batch: zebrafish functional xenograft vasculature platform (zFXVP). As proof of principle, we applied zFXVP to a small compound library which has been implicated in affecting the morphology of tumor vasculature. zFXVP identified PF-502 as a durable tumor vascular normalization agent. Further molecular analysis using RNA-Seq, pharmaceutical inhibition and gene knockout indicate PF-502 can induce endothelial cell cycle arrest and simplify redundant tumor vasculature by blocking PI3K/mTOR signaling and stabilize the vessel lumen and stimulate the blood function by activating Notch1 signaling with mediating S3 cleavage. Last, in mouse tumor xenograft model, PF-502 reproduced a potent vascular normalizing effect at a sub MTD (maximum tolerated dose) and showed its ability to improve intra-tumoral drug delivery and synergize chemotherapy, which confirms the reliability of zFXVP and implicates the potential application of PF-502 in clinical practice as an adjuvant vascular normalization drug.

2023-09-13 | GSE224106 | GEO

Heterogeneity of Breast Cancer Vasculature

2010-09-19 | GSE15363 | GEO