TGFA (Transforming Growth Factor Alpha)

These findings are highly relevant for clinicians and researchers aiming to enhance ICI effectiveness in solid tumors. Given the ongoing clinical evaluation of iRGD, this simple, non-conjugated strategy offers a feasible and rapidly translatable approach to overcome a key limitation of current ICI therapy and improve outcomes for patients with HCC.

The significant increases in serum PDGF-AA and TGF-α, and significant decreases in serum EGF and Flt3 ligand could be explained by post-procedural inflammatory or paraneoplastic mechanisms. Further research into these biomarkers with larger cohorts may enable further understanding of their role pre- and post-operatively in TTPB and their correlation with clinical outcomes. This may be used to develop a clinical tool to predict or identify patients at risk of early post-TTPB complications.

These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation.

In vivo, volasertib treatment attenuated fibroblast activation and collagen deposition during TGFα-induced pulmonary fibrosis. Together, these findings identify a pathogenic role for the WT1-MYCN-PLK1 axis in fibroblast activation and provide proof-of-concept evidence supporting PLK1 inhibition with volasertib as a potential therapeutic strategy for IPF.

Meanwhile, we found that BMI served as a mediator to mediate the causal effect between MAPK3 and KOA. Further experiments are needed in the future to verify the mechanism of action of the targets identified in this study in KOA.

gasseri significantly decreased the levels of the pro-inflammatory cytokine TNF and reduced immune cell infiltration in stained gastric tissues. Together, these findings suggest that certain lactobacilli can counteract the H. pylori-mediated induction of HBEGF and TGF-α expression, and indicate that ADAM17 could be targeted to inhibit the cancer-related effects of H. pylori.

These findings suggest that TGF-α drives BP pathogenesis by compromising cell adhesion and promoting tissue inflammation. Targeting TGF-α or its downstream effectors may offer novel therapeutic strategies for BP treatment.

Conclusion All experimental mice with a genotype of Pdx-Cre, TGFα, LSL-KRAS Mu/Wt developed a phenotype consistent with congenital choledochal cyst. This transgenic mouse model mimics the oncogenic nature of choledochal cyst and could be used to further study disease pathophysiology and novel interventions.

Drug repurposing identified 40 FDA-approved TGFA-targeting drugs; irinotecan exhibited the highest binding affinity (-62.0 kcal/mol) in docking studies. TGFA is a novel glioma susceptibility gene with subtype-specific expression. Its therapeutic targeting offers opportunities for precision therapy, potentially advancing glioma clinical management.

The monoclonal antibody Cetuximab, which blocks EGFR, has emerged as a highly effective treatment, capable of inducing clinical and histological remission...For patients with refractory symptoms, severe complications, or malignant transformation, surgical intervention via partial or total gastrectomy remains the definitive treatment. This review provides a detailed examination of the current understanding of the molecular underpinnings, diverse clinical spectrum, diagnostic modalities, and therapeutic landscape of MD.

Furthermore, Hh signaling was shown to play an important role in the pathogenesis of MD and may serve as a potential therapeutic target.

The selected EGFR-targeted P20 peptide was investigated by a wide range of in silico, in vitro, in vivo and ex vivo methods, allowing us to formulate the following main (1) P20 has a theoretical half-life of 100 h and binds to EGFR domains that harbor the EGF binding site; (1) the peptide binds in a higher level to cancer cells and tissues compared to healthy ones; (2) it induces EGFR endocytosis and follows the non-degradative EGFR intracellular pathway; (3) P20 does not interfere with EGF binding and acts as a non-competitive inhibitor of EGFR; (4) it could contribute to the therapeutic effect of anti-cancer drugs by decreasing the expression and activation of EGFR, as well as of AKT phosphorylation in ATC cells; (5) P20 does not induce in vivo toxic effects in the main tissues and organs; (6) it is concentrated in tumors, where the peptide is retained for longer time than in other tissues due to its binding to EGFR. Abbreviations: 7-AAD, 7-Aminoactinomycin D; AA%, amino acid composition expressed as a percentage; ABC, Avidin/Biotinylated enzyme Complex; ABTS, 2,2'-azino-bis-3-ethylbenzothioazoline-6-sulfonic acid; A.I., aliphatic index; AKT, protein kinase B; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATC, anaplastic thyroid carcinoma; Bad, the Bcl2 associated agonist of cell death protein; BCA, Pierce BiCinchoninic Acid; BUN, Blood Urea Nitrogen; CMMI, Center for Microscopy and Molecular Imaging; DAB, 3,3'-diaminobenzidine tetrahydrochloride solution; DAPI, 4',6-diamidino-2-phenylindole; DTT, dithiothreitol; ECACC, European Collection of Authenticated Cell Cultures; ECL, Enhanced chemiluminescence; ED, extracellular domain; ED-EGFR, Extracellular domain of EGFR; EGF, epidermal growth factor; EGFR, the epidermal growth factor receptor; ER, endoplasmic reticulum; FLI, Fluorescence Lifetime Imaging; GAPDH, the glyceraldehyde-3-phosphate dehydrogenase; IC50, the half-maximal inhibitory concentration; IF, immunofluorescence, IHC, immunohistochemistry; IL7R, interleukin 7 receptor; K*d, the apparent dissociation constant; LDS, lithium dodecyl sulfate sample buffer; MAPK, Mitogen-Activated Protein Kinase; mTOR, mammalian target of rapamycin; NA: not available; NMRI, The Naval Medical Research Institute (mouse model); NSP: non-stimulated cells incubated with P20-rhodamine; NSPE: non-stimulated cells incubated with P20-rhodamine and soluble EGFR; PAM, the PI3K/AKT/mTOR signaling pathway; PEG, polyethylene glycol; peptide-TR: peptide-rhodamine; PFBB, Protein-Free Blocking Buffer; PI3K, Phosphoinositide 3-kinase; PLCγ/PKC, phospholipase Cγ/protein kinase C; PMSF, phenylmethylsulphonyl fluoride; PS, phosphatidylserine; SP: cells stimulated with EGF and incubated with P20-rhodamine; SPE: cells stimulated with EGF and incubated with P20-rhodamine and soluble EGFR; RET, Rearranged during transfection; RRFL, Relative Ratio of Fluorescent Labeling; RRIL, Relative Ratio of IHC Labeling; RTK, receptor tyrosine kinases; SD: standard deviation; SDS: Sodium Dodecyl Sulfate; SI: signal intensity; T-Bil: total bilirubin; TC, thyroid carcinoma; T-Chol, Total cholesterol; TGF-α, Transforming growth factor alpha; TK, tyrosine kinase; TMB, 3,3',5,5'-Tetramethylbenzidine; VEGFR, Vascular Endothelial Growth Factor Receptor.