ABSTRACT
Exploring novel early detection biomarkers and developing more efficacious treatments remain pressing tasks in the current research landscape for hepatocellular carcinoma (HCC). Morphologically and molecularly separate from apoptosis, cell death, and autophagy, ferroptosis is a recently discovered, unique, controlled form of cell death. SLC7A11 (also known as xCT) represents a subunit of the cystine-glutamate antiporter (also known as system Xc(-)). A growing body of research suggests that induction of ferroptosis through SLC7A11 can effectively eliminate hepatocellular carcinoma (HCC) cells, particularly those exhibiting resistance to alternative forms of cell death. Thus, targeting ferroptosis via SLC7A11 may become a new direction for the design of therapeutic strategies for HCC. Although many research articles have investigated the possible roles of SLC7A11 in HCC, a study that summarizes the main findings, including the regulators and mechanisms of action of SLC7A11 in HCC is not available. Therefore, we present a comprehensive overview of the functions of ferroptosis, particularly SLC7A11, in the identification, development, and management of HCC in this review. In addition, we discuss how this knowledge can be translated into treatment by providing a systemic therapy in advanced HCC using sorafenib, the first-line drug targeting multiple kinases and SLC7A11. We further dissect the possible barriers as well as the corresponding solutions and provide insights on how to navigate effective treatment using this knowledge.
ABSTRACT
Background: HAUS Augmin-like complex subunit 1(HAUS1), as a controlling gene, which affected the production of spindle was firstly discovered in Drosophila cells. Although HAUS1 has been intensively studied, but its significance and relationship with the immune microenvironment in Hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: All data of HCC in this paper were obtained from The Cancer Genome Atlas(TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and the Human Protein Atlas(HPA) database. The role and potential value of HAUS1 in the tumorigenesis and development of HCC were studied by applying plenty of bioinformatics analysis methods. Knocked down the expression of HAUS1 through siRNA and further investigated the function of HAUS1 in HCC Results: HAUS1 was highly expressed in HCC, which led to a poor prognosis. ROC curve analysis showed that HAUS1 had a excellent diagnostic value. It was also associated with clinical stage, pathological grade and AFP of HCC. Univariate and multivariate COX regression analysis showed that HAUS1 was an independent prognostic factor for HCC patients. HAUS1 was associated with immune cells infiltrate and immune checkpoints in HCC, and it could generate significative therapeutic results when combined with anti-CTLA4 and anti-CD274 treatment. In vitro experiments, HAUS1 was found to promote the proliferation, invasion and metastasis, participated in cell cycle regulation and inhibited apoptosis of HCC. Conclusion: These results suggested that HAUS1 might serve as a potential therapeutic target, as well as a diagnostic, prognostic, and survival biomarker for HCC.
ABSTRACT
BACKGROUND: The optimal therapy for immunoglobulin A nephropathy (IgAN) remains uncertain. Leflunomide (LEF) is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes. Several clinical trials were designed to evaluate the efficacy of LEF, but their results were controversial. METHODS: Ovid Medline, Embase, the Cochrane Library, PubMed, and CNKI were systematically searched. Search terms included ("glomerulonephritis" OR "nephritis") AND ("immunoglobulin A" OR "IgA") AND "leflunomide". Studies in which patients were diagnosed with IgAN based on renal biopsy were included. Studies needed to report clinical outcomes via either short- or long-term clinical examination, remission rate, or complication rate. RESULTS: Forty-four studies encompassing 1802 patients were included, of which 35 were randomized controlled trials. Results of 24 h post-treatment urine protein tests and serum creatinine tests were significantly lower in patients treat with LEF and corticosteroids (CS) or valsartan (ACEI) (CS + LEF or CS + ACEI) compared with patients treated with CS or ACEI alone (P < 0.05). More patients treated with CS + LEF (31.2%) achieved complete remission (CR) than patients treated with CS alone (22.2%) (RR = 0.71, 95% CI 0.59-0.85, P < 0.05). Although there was no significant difference in CR between patients treated with cyclophosphamide and CS (CS + CTX) and those treated with CS + LEF, the complication rate in the former group was higher (28.4%) than in the latter one (11.4%) (RR = 2.46, 95% CI 1.47-4.13, P < 0.005). CONCLUSION: LEF appears to improve renal function while decreasing loss of urine protein. Combination regimens including LEF were better and safer compared with CS or ACEI alone or combinations including CTX.
