Riberhead1804

Of note, LINC01559 targeted both PGK1 and PTEN to promote GC progression by activating PI3K/AKT pathway. Taken together, our study demonstrated that LINC01559 accelerated GC progression via upregulating PGK1 and downregulating PTEN to trigger phosphatidylinositol 3-kinase/AKT serine/threonine kinase (PI3K/AKT) pathway, indicating LINC01559 as a potential biomarker for GC treatment.Tumor cells adapt their metabolism to meet the energetic and anabolic requirements of high proliferation and invasiveness. The metabolic addiction has motivated the development of therapies directed at individual biochemical nodes. However, currently there are few possibilities to target multiple enzymes in tumors simultaneously. Flavin-containing enzymes, ca. 100 proteins in humans, execute key biotransformations in mammalian cells. To expose metabolic addiction, we inactivated a substantial fraction of the flavoproteome in melanoma cells by restricting the supply of the FMN and FAD precursor riboflavin, the vitamin B2. Vitamin B2 deficiency affected stability of many polypeptides and thus resembled the chaperone HSP90 inhibition, the paradigmatic multiple-target approach. In support of this analogy, flavin-depleted proteins increasingly associated with a number of proteostasis network components, as identified by the mass spectrometry analysis of the FAD-free NQO1 aggregates. Proteome-wide analysis of the riboflavin-starved cells revealed a profound inactivation of the mevalonate pathway of cholesterol synthesis, which underlines the manifold cellular vulnerability created by the flavoproteome inactivation. Cell cycle-arrested tumor cells became highly sensitive to alkylating chemotherapy. Our data suggest that the flavoproteome is well suited to design synthetic lethality protocols combining proteostasis manipulation and metabolic reprogramming.cMYC (MYC) is a potent oncoprotein that is subject to post-translational modifications that affect its stability and activity. Here, we show that Serine 62 phosphorylation, which increases MYC stability and oncogenic activity, is elevated while Threonine 58 phosphorylation, which targets MYC for degradation, is decreased in squamous cell carcinoma (SCC). The oncogenic role of MYC in the development of SCC is unclear since studies have shown in normal skin that wild-type MYC overexpression can drive loss of stem cells and epidermal differentiation. To investigate whether and how altered MYC phosphorylation might affect SCC development, progression, and metastasis, we generated mice with inducible expression of MYCWT or MYCT58A in the basal layer of the skin epidermis. In the T58A mutant, MYC is stabilized with constitutive S62 phosphorylation. find more When challenged with DMBA/TPA-mediated carcinogenesis, MYCT58A mice had accelerated development of papillomas, increased conversion to malignant lesions, and increased metastasis as compared to MYCWT mice. In addition, MYCT58A-driven SCC displayed stem cell gene expression not observed with MYCWT, including increased expression of Lgr6, Sox2, and CD34. In support of MYCT58A enhancing stem cell phenotypes, its expression was associated with an increased number of BrdU long-term label-retaining cells, increased CD34 expression in hair follicles, and increased colony formation from neonatal keratinocytes. Together, these results indicate that altering MYC phosphorylation changes its oncogenic activity-instead of diminishing establishment and/or maintenance of epidermal stem cell populations like wild-type MYC, pS62-MYC enhances these populations and, under carcinogenic conditions, pS62-MYC expression results in aggressive tumor phenotypes.BACKGROUND Renal function is strongly associated with patient survival after liver transplantation. However, the estimated glomerular filtration rate (eGFR) after liver transplantation changes, especially in patients who receive diuretics or have urinary abnormalities. We aimed to elucidate how adjusting for these factors affecting eGFR predicted liver graft prognosis. MATERIAL AND METHODS This retrospective study included patients who underwent adult-to-adult living donor liver transplantation (LDLT) between 2000 and 2017. The factors affecting eGFR were assessed, and the association between eGFR and prognosis was investigated using Cox regression models after adjusting for factors affecting renal function. RESULTS We enrolled 244 patients. The median observation period was 4.6 years, and 88 patients reached graft loss or death with a functioning graft. One year after transplantation, 193 patients were living, and one-third of these showed improved eGFR; most of the patients with improved eGFR had taken diuretics before transplantation. A Cox regression model adjusted for the classical risk factors showed that donor age (P less then 0.001) and lower eGFR (P=0.02) were the independent risk factors associated with poor prognosis. After adjusting for diuretics and urinary abnormalities, eGFR was more strongly associated with liver graft prognosis (P=0.003). CONCLUSIONS Pre-transplant eGFR was associated with prognosis following LDLT and had a stronger effect on prognosis after adjusting for factors affecting eGFR.BACKGROUND Retinal vasoproliferative tumor (VPT) is a type of ocular vascular tumor that commonly occurs idiopathically and can be associated with secondary ocular diseases. Ocular albinism is an X-linked inherited disease and distinguished from oculocutaneous albinism by less hair and skin involvement. CASE REPORT A 42-year-old man with ocular albinism and moderate myopia presented with a history of insidious decrease in vision in both eyes over a period of months. On examination, the horizontal pendular nystagmus was present and diffuse iris transillumination defects were observed bilaterally. A fundus examination revealed a depigmented fundus with visible choroidal vessels, foveal hypoplasia, and a unilateral, elevated, vascular lesion in the superotemporal aspect of the retinal periphery. Optical coherence tomography of the lesion confirmed the retinal location and fluorescein fundus angiography indicated its vascular nature. B-scan ultrasonography was performed to measure the dimensions of the lesion. CONCLUSIONS Rare retinal VPT has been reported with systemic and ocular associations, but it has never been reported in the literature in association with ocular albinism.