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  • Tropomyosi http www apexbt com media

    2024-04-01

    Tropomyosin-related kinases (Trks) play crucial role in neurotrophin-mediated cellular activities, including neuronal differentiation, survival, and synaptic function [37] through activating downstream signaling mediators PI3K and Akt [38]. In a therapeutic context, Akt has been shown to mediate striking neurotrophic and anti-apoptotic effects in vivo [38]. The pro-survival effects of NGF are mediated by the TrkA and NGF activation of PI3K/Akt signaling can protect PC-12 cells upstream of mitochondrial outer membrane permeabilisation (MOMP) [39]. NGF is initially translated as a precursor, proNGF, which can be cleaved intracellularly into mature NGF by furin [40], extracellularly by plasmin or matrix metalloproteinases [13,41], or remain intact and signal in its precursor form [42,43]. Although both NGF and proNGF are able to bind to and activate TrkA and p75NTR, they do so with different affinities. TrkA has a higher affinity for mature NGF than for proNGF [42,43], while p75NTR has a higher affinity for proNGF than for mature NGF [13]. The ratio of TrkA to p75NTR affects whether proNGF and mature NGF signal cell survival or apoptosis. Under circumstances of loss in TrkA, which occurs in neurodegenerative disease or neuronal injury, proNGF, but not mature NGF, signaling switches from cell survival to cell death [44].
    Competing interests
    Funding
    Acknowledgment
    Introduction Glioma, which arises from glial cells, accounts for 80% of all malignant (3S,5S)-Atorvastatin sodium salt tumors [1]. The World Health Organization categorizes gliomas into four grades, of which glioblastoma multiforme (GBM) (grade IV) is the most common malignant primary brain tumor in adults. Although optimal multimodality treatments that typically include surgery, radiation, and cytotoxic chemotherapy are available, recent clinical trials have reported a median survival of only 14–16 months with a 2-year survival rate of about 30% [[2], [3], [4]]. The highly invasive nature of GBM cells that extravasate into surrounding brain parenchyma is a major cause of treatment failure and tumor recurrence [5]. Yet the molecular mechanisms underlying its regulation remain elusive. Therefore, a deeper understanding of the GBM biology, including identification of their cells of origin and relevant molecular events leading to invasion, is of particular clinical importance to develop effective therapies for GBM patients. Epithelial-mesenchymal transition (EMT) is a central process for normal embryonic development [6]. Recent evidence suggests that EMT is one of the most important molecular events in the invasion of tumors including GBM [[7], [8], [9]]. EMT can be a potential target for inhibiting the GBM invasion [[10], [11], [12]]. Therefore, understanding the molecular mechanism of EMT is crucial for the treatment of GBM. Downregulated renal cell carcinoma gene 1 (DRR1) is designated by Tohoku University cDNA clone A on chromosome 3 (TU3A) and also known as FAM107A [13]. DRR1 is considered as a candidate tumor suppressor gene because its expression is decreased in various types of cancer and its increased expression suppresses cancer cell proliferation and induces cell apoptosis [[14], [15], [16]]. DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis [17]. However, DRR1 was recently found to be highly expressed in the invasive component of GBM and thought to drive tumor invasion [[18], [19], [20]]. Therefore, DRR1 may have a dual function in the regulation of biological function, and thus may be important in the tumorigenesis and invasion of GBM.
    Materials and methods
    Results
    Discussion Predicting the clinical outcomes of cancer patients is very important and forms the foundation of personalized cancer therapy [27]. The overall survival of patients with high-grade gliomas varies from 1 week to a few years, suggesting that the clinical prognostic factors reach their limit in identifying prognostic subgroups for personalized treatment [[28], [29], [30]]. Nowadays, the most important prognostic factors affecting outcome in patients with high-grade glioma are age, tumor grade (anaplastic glioma versus GBM), Karnofsky performance status (KPS), and several molecular genetic alterations [[31], [32], [33]]. However, these factors may not accurately estimate prognosis in GBM patients because of patient heterogeneity, since the outcome in each grade is highly variable and genetic differences may also contribute to varying survival rates [[34], [35], [36]]. Moreover, regular treatments do not benefit all patients equally and adverse effects of treatments may also dramatically deteriorate the quality-of-life of some patients [37]. Thus, there is urgency in understanding the molecular factors involved in GBM prognosis, which may lead to new insights into accurate prognostic prediction that are critical to the selection of appropriate therapeutic approaches.