Frontiers in Endocrinology

Our medical research library holds 7 studies published in Frontiers in Endocrinology (2017–2024). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 7 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Frontiers Research Foundation]
• Published: 2010 to the present, Switzerland
• Language: English
• ISSN: 1664-2392 (electronic)
• Its record in the NLM Catalog

2020s

• Survival prediction in peritoneal mesothelioma: a nomogram based on SEER data and a Chinese cohort. Y. Fang, M. Xiang, Z. Jiang, et al. 2024;15:1432787. PubMed · Publisher · Free full text

  Abstract

  Objective: This study aimed to develop nomogram predicting overall survival (OS) of patients with peritoneal mesothelioma (PeM) using data from Surveillance, Epidemiology, and End Results (SEER) database and a Chinese institution.

  Methods: 1,177 PeM patients from the SEER database were randomized into training and internal validation cohorts at a 7:3 ratio. An external validation cohort consisting of 109 patients was enrolled from a Chinese institution. Nomogram was constructed based on variables identified through multivariate Cox regression analysis and evaluated by consistency indices (C-index), calibration plots, and receiver operating characteristic (ROC) curves. Patients were stratified into different risk categories, and Kaplan-Meier survival analysis was used to assess OS differences among these groups.

  Results: The nomogram, incorporating age, gender, histological type, T stage, M stage, and surgical status, demonstrated strong predictive capability with C-index values of 0.669 for the training cohort, 0.668 for the internal validation cohort, and 0.646 for the external validation cohort. The nomogram effectively stratified patients into high-risk and low-risk groups, with the high-risk group exhibiting significantly poorer OS (P < 0.05). Multivariate analysis confirmed gender, age, surgical intervention, and M stage as independent prognostic factors (P < 0.05). Specifically, male gender, older age, and unspecified M stage were linked to worse outcomes, while surgical intervention was associated with improved survival.

  Conclusion: The nomogram provide a reliable tool for predicting the survival in PeM patients, facilitating more informed treatment decisions. Key independent prognostic factors include gender, age, surgical intervention, and M stage.

  Copyright © 2024 Fang, Xiang, Jiang, Li, Yuan, Pei, Li and Sun.

• Establishment and validation of nomograms to predict survival probability of advanced malignant pleural mesothelioma based on the SEER database and a Chinese medical institution. X. Zhang, L. Chang, Y. Zhu, et al. 2023;14:1139222. PubMed · Publisher · Free full text

  Abstract

  Objective: The purpose of this study was to build nomograms for predicting the survival of individual advanced pleural mesothelioma (MPM) patients using the Surveillance, Epidemiology, and End Results (SEER) database.

  Methods: The 1251 patients enrolled from the SEER database were randomized (in a 7:3 ratio) to a training cohort and an internal validation cohort. Eighty patients were enrolled from the Harbin Medical University Cancer Hospital as the external validation cohort. Nomograms were constructed from variables screened by univariate or multivariate Cox regression analyses and evaluated by consistency indices (C-index), calibration plots, and receiver operating characteristic (ROC) curves. Patients from the SEER database who received chemotherapy alone and chemoradiotherapy were statistically paired using propensity score matching of the two groups and performed subgroup analysis in the screened variables.

  Results: The nomograms are well-structured and well-validated prognostic maps constructed from four variables: gender, histology, AJCC stage, and treatment. All individuals were allocated into high-risk versus low-risk groups based on the median risk score of the training cohort, with the high-risk group having worse OS and CSS in all three cohorts (P<0.05). The outcomes of the subgroup analysis indicated that the advanced MPM patients receiving chemotherapy with or without local radiotherapy do not affect OS or CSS.

  Conclusion: The accurate nomograms to predict the survival of patients with advanced MPM were built and validated based on an analysis of the SEER database with an external validation cohort. The study suggests that the additional local radiotherapy to chemotherapy does not increase the survival benefit of patients.

  Copyright © 2023 Zhang, Chang, Zhu, Mao, Zhang, Zhang and Wang.

• Obesity and risk for respiratory diseases: a Mendelian randomization study. W. Yang, Y. Yang, Y. Guo, et al. 2023;14:1197730. PubMed · Publisher · Free full text

  Abstract

  Background: No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases.

  Methods: BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method.

  Results: This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200).

  Conclusion: This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.

  Copyright © 2023 Yang, Yang, Guo, Guo, Ma and Han.

• Identification of glycolysis genes signature for predicting prognosis in malignant pleural mesothelioma by bioinformatics and machine learning. Y. Xiao, W. Huang, L. Zhang, et al. 2022;13:1056152. PubMed · Publisher · Free full text

  Abstract

  Background: Glycolysis-related genes as prognostic markers in malignant pleural mesothelioma (MPM) is still unclear. We hope to explore the relationship between glycolytic pathway genes and MPM prognosis by constructing prognostic risk models through bioinformatics and machine learning.

  Methods: The authors screened the dataset GSE51024 from the GEO database for Gene set enrichment analysis (GSEA), and performed differentially expressed genes (DEGs) of glycolytic pathway gene sets. Then, Cox regression analysis was used to identify prognosis-associated glycolytic genes and establish a risk model. Further, the validity of the risk model was evaluated using the dataset GSE67487 in GEO database, and finally, a specimen classification model was constructed by support vector machine (SVM) and random forest (RF) to further screen prognostic genes.

  Results: By DEGs, five glycolysis-related pathway gene sets (17 glycolytic genes) were identified to be highly expressed in MPM tumor tissues. Also 11 genes associated with MPM prognosis were identified in TCGA-MPM patients, and 6 (COL5A1, ALDH2, KIF20A, ADH1B, SDC1, VCAN) of them were included by Multi-factor COX analysis to construct a prognostic risk model for MPM patients, with Area under the ROC curve (AUC) was 0.830. Further, dataset GSE67487 also confirmed the validity of the risk model, with a significant difference in overall survival (OS) between the low-risk and high-risk groups (P < 0.05). The final machine learning screened the five prognostic genes with the highest risk of MPM, in order of importance, were ALDH2, KIF20A, COL5A1, ADH1B and SDC1.

  Conclusions: A risk model based on six glycolytic genes (ALDH2, KIF20A, COL5A1, ADH1B, SDC1, VCAN) can effectively predict the prognosis of MPM patients.

  Copyright © 2022 Xiao, Huang, Zhang and Wang.

• Calcitriol Inhibits Viability and Proliferation in Human Malignant Pleural Mesothelioma Cells. I. Gesmundo, F. Silvagno, D. Banfi, et al. 2020;11:559586. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor, often associated with exposure to asbestos and characterized by poor prognosis and limited treatment options. The biologically active form of vitamin D, calcitriol, exerts anticancer effects in many cell types, both alone and in combination with chemotherapy drugs, through binding to vitamin D receptor (VDR); however, the role of calcitriol in MPM is still unknown. This study aimed to determine the potential antitumor role of calcitriol in MPM. The results showed that calcitriol reduces cell viability and proliferation in human MPM cells lines, which express both cytoplasmic and nuclear VDR; furthermore, calcitriol potentiated the inhibitory activity of the chemotherapy drug PEM. These effects were paralleled by cell cycle arrest and inhibition in expression of c-Myc and cyclins involved in cell cycle progression. Exposure of MPM cells to calcitriol also produced an alteration in mitochondrial function and inhibition in the expression of respiratory chain complex subunits. Finally, the inhibitory effects of calcitriol were also observed on viability of human primary MPM cells. Collectively, these results indicate a novel anticancer role for calcitriol in MPM, suggesting potential for vitamin D derivatives, alone or in combination with chemotherapy, in the treatment of this malignancy.

  Copyright © 2020 Gesmundo, Silvagno, Banfi, Monica, Fanciulli, Gamba, Congiusta, Libener, Riganti, Ghigo and Granata.

2010s

• When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?. A.M. Baird, D. Easty, M. Jarzabek, et al. 2019;10:89. PubMed · Publisher · Free full text

  Abstract

  Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.

• Environmental Factors Impacting Bone-Relevant Chemokines. J.T. Smith, A.D. Schneider, K.M. Katchko, et al. 2017;8:22. PubMed · Publisher · Free full text

  Abstract

  Chemokines play an important role in normal bone physiology and the pathophysiology of many bone diseases. The recent increased focus on the individual roles of this class of proteins in the context of bone has shown that members of the two major chemokine subfamilies-CC and CXC-support or promote the formation of new bone and the remodeling of existing bone in response to a myriad of stimuli. These chemotactic molecules are crucial in orchestrating appropriate cellular homing, osteoblastogenesis, and osteoclastogenesis during normal bone repair. Bone healing is a complex cascade of carefully regulated processes, including inflammation, progenitor cell recruitment, differentiation, and remodeling. The extensive role of chemokines in these processes and the known links between environmental contaminants and chemokine expression/activity leaves ample opportunity for disruption of bone healing by environmental factors. However, despite increased clinical awareness, the potential impact of many of these environmental factors on bone-related chemokines is still ill defined. A great deal of focus has been placed on environmental exposure to various endocrine disruptors (bisphenol A, phthalate esters, etc.), volatile organic compounds, dioxins, and heavy metals, though mainly in other tissues. Awareness of the impact of other less well-studied bone toxicants, such as fluoride, mold and fungal toxins, asbestos, and chlorine, is also reviewed. In many cases, the literature on these toxins in osteogenic models is lacking. However, research focused on their effects in other tissues and cell lines provides clues for where future resources could be best utilized. This review aims to serve as a current and exhaustive resource detailing the known links between several classes of high-interest environmental pollutants and their interaction with the chemokines relevant to bone healing.

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