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Objectives: Liquid biopsy, with its noninvasive nature and ability to detect tumor-specific genetic alterations, emerges as an ideal biomarker for monitoring recurrences for locally advanced rectal cancer (LARC). Completed studies have small sample sizes and different experimental methods. To consolidate and assess the collective evidence regarding the prognostic role of circulating DNA (ctDNA) detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT).
Methods: Computerized bibliographic searches of MEDLINE and CANCERLIT (2000 to 2023) were supplemented with hand searches of reference lists. Study selection: studies evaluating oncological outcomes of patients with LARC treated with a nCRT comparing patients with positive and negative liquid biopsy at baseline and after nCRT. Data extraction: data on population, intervention, and outcomes were extracted from each study, in accordance with the intention to treat method, by 2 independent observers, and combined using the DerSimonian method and Laird method.
Results: Nine studies follow inclusion criteria including 678 patients treated with nCRT. The pooled RD rate of ctDNA negative between measure at baseline and after nCRT is statistically significant 61% (95% CI: 53-70, P =0.0002). The hazard ratio (HR) of progression-free survival between ct-DNA negative and positive is significant 7.41 (95% CI: 4.87-11.289, P <0.00001).
Conclusions: ctDNA can identify patients with different recurrence risks following nCRT and assess prognosis in patients with LARC. Further prospective study is necessary to determine the utility of ctDNA in personalised therapy for patients with LARC.
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http://dx.doi.org/10.1097/COC.0000000000001148 | DOI Listing |
PLoS One
September 2025
Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany.
Background: Current aftercare in breast cancer survivors aims to detect local recurrences or contralateral disease, while the detection of distant metastases has not been a central focus due to a lack of evidence supporting an effect on overall survival. However, the data underpinning these guidelines are mainly from trials of the 1980s/1990s and have not been updated to reflect the significant advancements in diagnostic and therapeutic options that have emerged over the past 40 years. In this trial, the aim is to test whether a liquid biopsy-based detection of (oligo-) metastatic disease at an early pre-symptomatic stage followed by timely treatment can impact overall survival compared to current standard aftercare.
View Article and Find Full Text PDFNeuroendocrinology
September 2025
Introduction Neuroendocrine tumors (NETs) are a rare and heterogeneous group of neoplasms with both clinical and genetic diversity. The clinical applicability of molecular profiling using liquid biopsy for identifying actionable drug targets and prognostic indicators in patients with advanced NETs remains unclear. Methods In this study, we utilized a custom-made 37 genes panel of circulating tumor DNA (ctDNA) based on next-generation sequencing (NGS) in 47 patients with advanced NETs.
View Article and Find Full Text PDFToxicol Sci
September 2025
Department of Pharmacology, Rutgers University Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Neutrophils play a complex role in the pathogenesis of chronic liver disease and have been linked to both liver damage and injury resolution. Recent reports propose that neutrophils drive liver injury and fibrosis through the formation of neutrophil extracellular traps (NETs). This study tests the hypothesis that the enzyme peptidyl arginine deiminase-4 (PAD4) drives NET formation and liver fibrosis in experimental chronic liver injury.
View Article and Find Full Text PDFJCI Insight
September 2025
Division of Nephrology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States of America.
Background: Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects that attenuate acute kidney injury (AKI) in animal models.
Methods: We conducted a phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among 150 critically ill adult patients at high-risk of moderate-to-severe AKI. The primary endpoint was a hierarchical composite of death, kidney replacement therapy (KRT), and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure.
Nucleic Acids Res
September 2025
Division of Chromatin Regulation, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, is catalyzed by Clr4/Suv39. Clr4/Suv39 contains two conserved domains-an N-terminal chromodomain and a C-terminal catalytic domain-connected by an intrinsically disordered region (IDR). Several mechanisms have been proposed to regulate Clr4/Suv39 activity, but how it is regulated under physiological conditions remains largely unknown.
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