Publications by authors named "E Mihara"
Background: This study aimed to develop a therapeutic agent promoting teeth regeneration from autologous tissues for congenital tooth agenesis, specifically for hypodontia (≤5 missing congenital teeth, 10% prevalence) and oligodontia (≥6 missing congenital teeth, 0.1% prevalence).
Highlight: We studied mice genetically deficient in the USAG-1 protein, an antagonist of BMP/Wnt which forms excessive teeth.
The regenerative functions associated with cytokines and growth factors have immense therapeutic potential; however, their poor pharmacokinetics, resulting from structural features, hinder their effectiveness. In this study, we aimed to enhance the pharmacokinetics of growth factors by designing receptor-binding macrocyclic peptides through mRNA display and grafting them into loops of immunoglobulin's crystallizable region (Fc). As a model, we developed peptide-grafted Fc proteins with hepatocyte growth factor (HGF) functionality that exhibited a prolonged circulation half-life and could be administered subcutaneously.
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- Semaphorin-plexin signaling, particularly through Semaphorin 4D (SEMA4D) and its receptor Plexin-B1 (PLXNB1), plays a critical role in regulating the tumor microenvironment (TME) and is linked to cancer progression, specifically in triple-negative breast carcinoma.
- In experiments with PLXNB1-deficient mice, researchers observed a significant reduction in tumor growth and metastasis, increased survival rates, and changes in immune cell behavior, leading to a more effective anti-tumor immune response.
- Targeting PLXNB1 not only reprogrammed the TME to enhance the efficacy of immunotherapy (specifically anti-PD-1 treatment) but also positions PLX
Overexpression of human epidermal growth factor receptor 2 (HER2) in breast and gastric cancers is associated with a poor prognosis, making it an important therapeutic target. Here, we establish a novel cancer-specific anti-HER2 antibody, HMab-214. HMab-214 reacts with HER2 on cancer cells, but unlike the therapeutic antibody trastuzumab, it does not react with HER2 on normal cells in flow cytometry measurements.
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- Short half-lives and poor blood-brain barrier transport limit the effectiveness of cytokines and growth factors as receptor agonists.
- A new method called 'lasso-grafting' was used to genetically engineer macrocyclic peptide pharmacophores into the Fc region of human immunoglobulins, improving their stability and transport to the brain.
- These engineered proteins successfully mimicked the effects of natural ligand-induced biological responses and showed enhanced brain accumulation in experimental models, suggesting potential for improved protein therapeutics.