Epigenetic perspectives on systemic autoimmune disease.

Evidence of epigenetic alterations in thrombosis and coagulation: A systematic review.

Type I interferon gene expression in antiphospholipid syndrome: Pathogenetic, clinical and therapeutic implications

Antiphospholipid syndrome (APS) is a rare heterogenous disorder associated with the presence of antiphospholipid antibodies and can present in a wide variety of clinical manifestations including thrombosis and pregnancy complications. Although the etiology of APS remains poorly understood, there is strong support for considering APS as a complex genetic disease in which multiple genetic risk factors, in conjunction with environmental factors, affect its onset, progression, and severity. Here, we provide a comprehensive review of the current knowledge of the genetic basis of APS, which remains in its infancy. Most genetic studies to date in APS were performed in small cohorts of patients. As a result, only few genetic associations reported are convincing. Several reports suggested genetic associations with HLA class II alleles in APS, and only two genetic loci outside of the HLA region (STAT4 and C1D) reached the threshold for genome-wide level of significance (P < 5 × 10−8). In this review, we also shed light on the genetic differences among the diverse clinical subsets of APS and briefly discuss the role that DNA methylation changes might play in the pathophysiology of this disease. The genetic basis of APS remains poorly characterized. Larger collaborative multicenter studies using well-characterized patients are needed to comprehensively understand the role of genetic susceptibility in APS.

Genetics of Antiphospholipid Syndrome

Epigenetics-mediated pathological alternations and their potential in antiphospholipid syndrome diagnosis and therapy.

Differential CpG methylation of the promoter of interleukin 8 and the first intron of tissue factor in Antiphospholipid syndrome.

Radiation therapy (RT) is an essential component in the therapeutic treatment of patients with localized prostate cancer (LPCa). Besides its local effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation. The present study explored the effect of RT on the T-cell receptor variable β (TCR Vβ) chain repertoire of peripheral blood T cells in patients with LPCa. High-throughput TCR Vβ sequencing was performed on 20 blood samples collected from patients with LPCa at baseline and 3 months post-RT. The diversity index was altered, as were TCR Vβ clonal evenness and convergence before and post-RT; however, these findings were not significant. Notably, marked changes in the frequencies among the top 10 TCR Vβ clonotypes were detected and some patients developed new clonotypes of high abundance. These data provided initial evidence that RT in patients with LPCa may induce systemic immune changes, which could be exploited by future therapies for improved clinical results.

https://www.spandidos-publications.com/10.3892/ijo.2022.5361/download

The impact of radiation therapy on the TCR Vβ chain repertoire in patients with prostate cancer

Pancreatic cancer is currently the seventh leading cause of cancer-related deaths worldwide, with the estimated death toll approaching half a million annually. Pancreatic ductal adenocarcinoma (PDAC) is the most common (>90% of cases) and most aggressive form of pancreatic cancer, with extremely poor prognosis and very low survival rates. PDAC is initiated by genetic alterations, usually in the oncogene KRAS and tumor suppressors CDKN2A, TP53 and SMAD4, which in turn affect a number of downstream signaling pathways that regulate important cellular processes. One of the processes critically altered is autophagy, the mechanism by which cells clear away and recycle impaired or dysfunctional organelles, protein aggregates and other unwanted components, in order to achieve homeostasis. Autophagy plays conflicting roles in PDAC and has been shown to act both as a positive effector, promoting the survival of pancreatic tumor-initiating cells, and as a negative effector, increasing cytotoxicity in uncontrollably expanding cells. Recent findings have highlighted the importance of cancer stem cells in PDAC initiation, progression and metastasis. Pancreatic cancer stem cells (PaCSCs) comprise a small subpopulation of the pancreatic tumor, characterized by cellular plasticity and the ability to self-renew, and autophagy has been recognised as a key process in PaCSC maintenance and function, simultaneously suggesting new strategies to achieve their selective elimination. In this review we evaluate recent literature that links autophagy with PaCSCs and PDAC, focusing our discussion on the therapeutic implications of pharmacologically targeting autophagy in PaCSCs, as a means to treat PDAC.

https://www.frontiersin.org/articles/10.3389/fonc.2022.1049436/pdf

Targeting autophagy in pancreatic cancer: The cancer stem cell perspective

The authors wish to make the following corrections to this paper [...]

P. Kogionou

Papers

Differential CpG methylation of the promoter of interleukin 8 and the first intron of tissue factor in Antiphospholipid syndrome.

The impact of radiation therapy on the TCR Vβ chain repertoire in patients with prostate cancer

Targeting autophagy in pancreatic cancer: The cancer stem cell perspective

Correction: Kogionou et al. Radiotherapy-Related Gene Signature in Prostate Cancer. Cancers 2022, 14, 5032