Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA352051 | ENA |
REPOSITORIES: ENA
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Project description:Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. We report here that tumor-infiltrating mast cells (MC) are powerful mediators decreasing efficacy of AAT in mice and cancer patients. They act in a cell-extrinsic manner by secreting granzyme B, which liberates pro-angiogenic mediators from the extracellular matrix. In addition, MC also diminish efficacy of anti-angiogenic agents in a cell-autonomous way, which can be blocked by the mast cell degranulation inhibitor cromolyn. Our findings are relevant in humans because patients harboring higher numbers of MC in their tumors have an inferior outcome after anti-angiogenic treatment in the Gepar Quinto randomized Phase 3 clinical trial. Thus, MC-targeting might represent a novel promising approach to increase efficacy of AAT.
2017-09-15 | GSE89395 | GEO
Project description:Mast cells are phenotypically and functionally highly heterogeneous, and their state is possibly controlled by their local microenvironment. Therefore, concrete analyses are needed to understand whether mast cells act as powerful motivators or dispensable bystanders in specific diseases. Here, we evaluated the correlation between synovial mast cells and rheumatoid arthritis (RA) disease severity, and the efficacy of therapeutic interventions against mast cells. We showed that degranulation of mast cells in inflammatory synovial tissues of RA patients was induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II (MHC II) and costimulatory molecules on mast cells were upregulated. These unique signaling response led to mast cell activation and promoted T cell responses, resulting in the progression of RA. Collagen-induced arthritis mouse models treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, showed significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to RA and may provide a novel mast cell-targeting therapy for RA.
2024-01-07 | PXD038584 | Pride
Project description:This model is based on:
Reinforcement learning-based control of tumor growth under anti-angiogenic therapy
Authors: Parisa Yazdjerdi, Nader Meskin, Mohammad Al-Naemi, Ala-Eddin Al Moustafa, Levente Kovacs
Abstract:
Background and objectives: In recent decades, cancer has become one of the most fatal and destructive diseases which is threatening humans life. Accordingly, different types of cancer treatment are studied with the main aim to have the best treatment with minimum side effects. Anti-angiogenic is a molecular targeted therapy which can be coupled with chemotherapy and radiotherapy. Although this method does not eliminate the whole tumor, but it can keep the tumor size in a given state by preventing the formation of new blood vessels. In this paper, a novel model-free method based on reinforcement learning (RL) framework is used to design a closed-loop control of anti-angiogenic drug dosing administration.
Methods: A Q-learning algorithm is developed for the drug dosing closed-loop control. This controller is designed using two different values of the maximum drug dosage to reduce the tumor volume up to a desired value. The mathematical model of tumor growth under anti-angiogenic inhibitor is used to simulate a real patient.
Results: The effectiveness of the proposed method is shown through in silico simulation and its robustness to patient parameters variation is demonstrated. It is demonstrated that the tumor reaches its minimal volume in 84 days with maximum drug inlet of 30 mg/kg/day. Also, it is shown that the designed controller is robust with respect to ± 20% of tumor growth parameters changes.
Conclusion: The proposed closed-loop reinforcement learning-based controller for cancer treatment using anti-angiogenic inhibitor provides an effective and novel result such that with a clinically valid and safe dosage of drug, the volume reduces up to 1mm3 in a reasonable short period compared to the literature.
2024-09-02 | BIOMD0000000821 | BioModels
Project description:Anti-angiogenic therapy is commonly used for the treatment of CRC. Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to anti-angiogenic therapy. MET is upregulated in response to VEGF pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study we set out to determine the efficacy of cabozantinib in a preclinical CRC PDTX model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated. CRC PDTX Model treated with cabozantinib
2014-08-30 | E-GEOD-60939 | biostudies-arrayexpress
Project description:Profiling of Granzyme B Secreting B cells
| PRJNA517914 | ENA
Project description:Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’).
2012-04-01 | GSE18804 | GEO
Project description:Targeting metabolic symbiosis to overcome resistance to anti-angiogenic therapy
| PRJNA313284 | ENA
Project description:The transcription factor β-catenin has been shown to be active in different types of dendritic cells (DCs) with ability to induce tolerogenic or anti-inflammatory features. Monocyte-derived dendritic cells (moDCs) have been widely used in dendritic cell-based cancer therapy, but so far with limited clinical efficacy. It is possible that aberrant differentiation or induction of dual pro- and anti-inflammatory features may decrease the moDCs efficiency to stage the immune attack on cancer cells. Here we show, using moDCs derived from healthy buffycoats, that β-catenin is detectable in both immature and lipopolysaccharide (LPS)-matured DCs.
2020-02-21 | E-MTAB-8330 | biostudies-arrayexpress
Project description:Increased expression of mast cell related genes in melanoma tumors obtained from humanized mice after anti-PD-1 therapy.
2020-12-07 | GSE161351 | GEO
Project description:Angiogenesis inhibitors are important for cancer therapy, but clinically approved anti-angiogenic agents have shown only modest efficacy and can compromise wound healing. This necessitates development of novel anti-angiogenesis therapies. we show significantly increased genes expression in tumor- versus wound or normal endothelial cells. Using a series of in vitro and in vivo studies with orthotopic and genetically engineered mouse models, we demonstrate the mechanisms by which it stimulates tumor angiogenesis. In contrast to its antagonistic effects on tumor angiogenesis, target blockage did not affect normal wound healing. These findings have significant implications for development of anti-angiogenesis therapies.
2017-10-21 | GSE105437 | GEO