Clusterin is a glycoprotein that has been implicated in many processes, including apoptosis, cell cycle regulation and DNA repair. Since clusterin expression has also been associated with tumorigenesis and the progression of various malignancies including prevalent tumors like prostate, colon, bladder and breast, this protein has been proposed as a good candidate for future treatments. There have been numerous studies conducted in cell lines and xenograft models with successful results that, in general, justify the use of clusterin as a therapeutic target. However, it is still necessary to continue with these studies in order to achieve a better understanding of the role of this protein in carcinogenesis and to determine those specific situations in which its therapeutic use may be more favorable. In this review, we will make a brief description of clusterin structure and genetics, its implication in tumorigenesis and cancer progression and its prognosis utility. Finally, we will analyze the effects of clusterin inhibition in different types of cancer.
Clusterin is a multifunctional glycoprotein whose role in cells has generated a great controversy in recent years. Since its discovery, numerous studies have linked clusterin expression deregulation with various physio-pathological processes such as cancer or Alzheimer's disease. Although the results of such investigations have sometimes been contradictory, mainly due to the dichotomous role of clusterin isoforms, it has been demonstrated that this protein is involved in diverse cellular processes, including apoptosis, cell cycle regulation, DNA repair or the acquisition of cell resistance against multiple conventional therapies. These results, together with the breakthrough of gene therapies, have motivated a great effort to elucidate the importance of clusterin as a potential therapeutic target. However, the understanding of a single gene, with multiple RNA transcripts and several protein isoforms has turned out to be a complex task. In this review, we summarize the studies published to date on factors that can affect clusterin expression and evaluate if a better understanding of this complex gene/protein would be useful to develop new treatment strategies for cancer and other pathologies.
e21603 Background: Despite the efforts, there is still no biomarker that is able to predict the response and / or that can be used in the monitoring of patients treated with check-points inhibitors (ICI). Methods: Prospective study of a panel of blood biomarkers that help predict the response to ICI treatments. Since June 2019, a total of 60 patients with non-small cell lung cancer (NSCLC) or melanoma have been included. Prior to the start of treatment (T1 moment), after the first cycle of ICI (T2), and to progression (Tp) or 6 months after the start, blood sample has been drawn to the patients and the analysis has been carried out by flow cytometry of the percentage of lymphocytes CD8, CD3, Treg, Myeloids, NK and B lymphocytes. The one.way statistical test has been carried out that allows us to see the effect of the response on the variable at each time. Results: Of the 60 patients included, we have radiological assessment in 38. 80% are patients with NSCLC. In the evaluation at 8-10 weeks we found stable disease / partial response in 25 patients (66%), 8 progressions (21%) and 2 unknown reevaluations (13%). A significant increase in CD3, CD8, CD4, and B lymphocytes was observed in responders (p < 0.005); however, an increase in NK was observed in patients in progression (p < 0.02). No significant differences in Treg have been described and the result related to myeloid cells is pending analysis. Conclusions: Our results open a door to peripheral blood monitoring as a new tool for the management of ICI. However, our data are preliminary, having not yet reached the expected sample size and with aspects that we must clarify as the increase in NK in progressors. In addition, the final objective of this study is to generate a score combining several biomarkers of blood and tissue to be used as a predictor of response to ICI (data pending analysis).
Objective The aim of this study was to determine the prevalence and type of thyroid hormone levels alterations in patients with acute pancreatitis (AP) and analyze if variations are useful AP progression predictors. Methods Three groups of patients were analyzed: AP patients (n = 90), abdominal pain patients (n = 30), and healthy control subjects (n = 40). Usual blood parameters for AP diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels were analyzed. Results Thyroid hormone level alterations were detected only within the AP group (41% of total cases), being the reduction in T3 levels the most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases). Alterations were not influenced by age or sex. Free thyroxine average values were also significantly higher in the AP group, compared with the healthy control group (P = 0.0005), resulting as independent predictors of both severity and mortality. Mortality in this group was 50%, with deceased patients showing FT4 levels above the reference limit. Conclusions Our results show that FT4 level determination during the initial clinical evaluation of patients admitted to the emergency service with AP can be included as a severity indicator to help determine the differential care of these cases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.