The successful treatment of the keloids is a big challenge in the plastic surgery field. The activation of the transcription factor 3 (ATF3) is discovered as a reactive adaptive gene, which plays a vital role in the activation of fibroblasts. This study aimed to investigate the expression and biological role of the ATF3 in the pathogenesis of the keloids. The ATF3 expression in normal skin and keloids was evaluated by real-time PCR, Western blot and immunohistochemistry.
The effects of the ATF3 on cell growth, apoptosis, invasion and collagen production were evaluated in overexpressive or ATF3 keloid fibroblast cells. The ATF3 expression has been considerably high in the keloid tissues compared to that of normal skin and parakelated cutaneous tissues. In addition, ATF3 promoted cell proliferation and collagen production in the Keloid fibroblast cells. Conversely, transfection with targeting has resulted in a decrease in cell viability and collagen synthesis by inhibiting the transformation-β1 growth factor (TGF-β1) and the 2/8 fibroblast growth factor ( FGF2 / 8) Production in kelooid fibroblasts. ATF3 could reduce the apoptosis rate of the keloid fibroblast cells.
Molecularment, we found that the ATF3 promoted the level of BCL2 and inhibit the expression of the associated agonist of cell death (ADB), Caspase3 and Caspase9 in the keloid fibroblast cells. ATF3 has also improved the invasive potential by improving the expression of family members of matrix metalloproteinases. ATF3 could induce an activation of the TGF-β / smad signaling channel in fibroblasts. Collectively, ATF3 could promote growth and invasion and inhibit apoptosis via a TGF-β / smad channel in keloid fibroblast cells, suggesting that AF3 could be considered a new therapeutic target for keeloid management.
Effect of Fibroblast Growth Factor 2 on Chondrocyte Degenerative Final Plate: Catabolism Anabolism
Background: The degeneration of the final plate is characterized by an imbalance between the anabolism and the catabolism of the chondrocyte of the final plate (CH). The fibroblast growth factor 2 (FGF2) has been demonstrated to promote cartilage repair by increasing the anabolic activity of the articular ch. We aim to explore the effect of FGF2 on the metabolism of the final plate CH to elucidate if the FGF2 could be used as therapy to delay the degeneration of the final plate.
Methods: We have collected the fabric of the patient final plate and tested the collagen II mRNA level as an anabolic marker and the expression of MMP-13 and TIP-4 as catabolic markers. The FGF2, FGF 1 (FGFR1) receiver and the expression of the FGFR3 mRNA of the final plate fabric were also analyzed. In addition, we treated the CHS with an exogenous FGF2 protein, measured the markers mentioned above, the proliferation and apoptosis of the CHS. To compare the effect of FGF2 on CHS with or without degeneration, we also induced the degeneration of CHS by interleukin-1β stimulation (IL-1β) and used the FGF2 protein to treat degenerative CHS.
Results: The extremely degenerative final plate presented a lower level of collagen II and TIMP-4, but expressed a more massive amount of MMP-13, FGF2 and FGFR1. FGF2 supplement regulated by the expression of FGFR1 / FGFR3, TIP-4, Collagen II and favored the proliferation of CHS. In the first 24 h of IL-1β treatment, the expression of the FGF2 mRNA has been removed, but it has increased considerably from 48 hours later. Meanwhile, the FGFR1 has been regulated and FGFR3 has been inhibited by IL-1β treatment. Interestingly, the FGF2 protein supplement has accelerated degenerative catabolism by decreasing the expression of collagen II and TIPM-4, but increases MMP-13. However, the FGF2 could promote the process of anabolism in case of blocking FGFR1. The FGF2 supplement could also promote proliferation and inhibited apoptosis of degenerative CHS, which could be amplified by blocking FGFR1.
Activating transcription factor 3 (ATF3) Regulates Cell Growth, Apoptosis, Invasion and Collagen Synthesis in Keloid Fibroblast through Transforming Growth Factor beta (TGF-beta)/SMAD Signaling Pathway
Fibroblast Growth Factor Receivers in Cancer: Genetic Alterations, Diagnostics, Therapeutic Targets and Resistance Mechanisms
Fibroblast growth factor (FGFRS) receptors are activated abandally activated by monocleotide variants, gene mergers and copy number amplifications in 5 to 10% of all human cancer, although this frequency increases to 10- 30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic modifications identified in human cancer and current challenges associated with the development of clinical quality molecular diagnostic tests for accurately detecting these changes in patients’ tissue and blood. The last decade has experienced significant progress in the development of FGFR targeted therapies, which include selective, non-selective and covalent molecule covalent inhibitors, as well as monoclonal antibodies against receptors.
We describe the expanding landscape of anti-FGFR therapies that are evaluated in early phase and randomized controlled clinical trials, such as Erdifineib and Pemigatinib, which are approved by the Food and Medicine Administration for the treatment of carcinoma. Urothelial mutated of the FGFR3 and FGFR2-Cholangiocarcinoma Fusion, respectively. However, despite the initial sensitivity to the inhibition of the FGFR, the drug resistance acquired to the progression of cancer develops in most patients. This phenomenon emphasizes the need to clearly define the mechanisms of resistance of tumor tumors and extrinsic tumor to facilitate the development of second-generation FGFR inhibitors and new treatment strategies beyond the progression of targeted therapy.
The treatment of metastatic melanoma has changed dramatically over the past decade with the introduction of targeted immunotherapy and therapy. Futile disease in the past is now treated with various options, resulting in improved survivors without progression and global, as well as improving the quality of life. That said, the majority of patients with metastatic melanoma end up succumbing to the disease.
Felicia
