High-Throughput Quantification of miRNA-3'-Untranslated-Region Regulatory Effects.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally, primarily through binding sites in 3' untranslated regions (3' UTRs). While computational and biochemical approaches have been developed to predict miRNA binding sites on target messenger RNAs, reliable and high-throughput assessment of the regulatory effects of miRNAs on full-length 3' UTRs can still be challenging. Utilizing a miniaturized and high-throughput reporter assay, we present a 'pilot miRNA-targeting map', containing 4,994 successfully measured miRNA:3' UTR regulatory outputs by pairwise assays between 461 miRNAs and eleven 3' UTRs.

Postcholecystectomy Gut Microbiome Changes and the Clinical Impact: A Systematic Review With Narrative Synthesis.

Background: Cholecystectomy (CCE) can affect the enterohepatic circulation of bile acids and result in gut microbiome changes. This systematic review aimed to clarify the effect of CCE on gut microbiome composition and its clinical impact.

Method: A systematic search was conducted in PubMed, Web of Science, and Scopus, combining keywords such as "cholecystectomy" or "post-cholecystectomy" with "gut microbiome," "stool microbiome," or "gut dysbiosis.

Second-line therapies in advanced hepatocellular carcinoma following first-line atezolizumab and bevacizumab: multicenter single institution cohort experience.

Background: Atezolizumab plus bevacizumab (A/B) received FDA approval as the first-line therapy for patients with advanced hepatocellular carcinoma (HCC) in 2020. However, optimal subsequent treatment options are unclear. Here, we describe clinical outcomes of advanced HCC patients following first-line treatment with A/B.

Allogeneic Hematopoietic Cell Transplantation in Elderly Patients in a Latin American Country: Analysis of 11 Year of Data from the Brazilian Registry SBTMO/CIBMTR.

This study analyzed recent changes in the utilization of allogeneic hematopoietic cell transplantation (HCT) for treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative diseases (MPDs) and the survival of HCT recipients ≥60 years of age in Brazil. This retrospective registry study included patients who received a first allogeneic HCT from any donor between 2012 and 2023. Of the 6657 patients, 444 (7%) were 60 years of age or older who received grafts from human leukocyte antigen (HLA)-matched related (42%) or unrelated (20%) donors or HLA-haploidentical donors (32%).

TBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach.

Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism.

Tumor sequencing before and after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: Genetic tumor characterization and clinical outcome.

Background And Purpose: Neoadjuvant chemoradiotherapy (NCRT) is a standard treatment option for locally advanced rectal cancer. However, there is still conflicting data about the genetic landscape and potential dynamics during and after NCRT. This study evaluated oncogenic driver mutations before NCRT and investigated corresponding resection samples after treatment.

Surgery/non-surgery-based strategies for invasive locally-advanced non-small cell lung cancer in the era of precision medicine.

Background: Treatments for invasive T non-small cell lung cancer (NSCLC) tumors have been traditionally individualized and often require multidisciplinary team (MDT) evaluation. Advances in precision medicine may open up new opportunities for these patients.

Methods: This retrospective cohort study, using the Surveillance, Epidemiology, and End Results (SEER) database, identified TNM NSCLC patients with central structure invasion from 2010 to 2020.

The C5a/C5aR1 axis promotes migration of tolerogenic dendritic cells to lymph nodes, impairing the anticancer immune response.

The precise mechanisms by which the complement system contributes to the establishment of an immunosuppressive tumor microenvironment (TME) and promotes tumor progression remain unclear. In this study, we investigated the expression and function of complement C5a receptor 1 (C5aR1) in human and mouse cancer-associated dendritic cells (DCs). First, we observed an overexpression of C5aR1 in tumor-infiltrating DCs, compared to DCs from blood or spleen.

Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Characterization of tumor microenvironment and cell interaction patterns in testicular and diffuse large B-cell lymphomas.

The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular DLBCLs (T-DLBCL) using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAMs) and cytotoxic tumor-infiltrating T cells (TILs) were characteristic of ABC DLBCL TME.

Development of a fibrin-targeted theranostic for gastric cancer.

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores.

Exploring aggregation genes in a chronic infection model.

Unlabelled: Bacterial aggregates are observed in both natural and artificial environments. In the context of disease, aggregates have been isolated from chronic and acute infections. () aggregates contribute significantly to chronic infections, particularly in the lungs of people with cystic fibrosis (CF).

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Fluorinated polyethyleneimine vectors with serum resistance and adjuvant effect to deliver LMP2 mRNA vaccine for nasopharyngeal carcinoma therapy.

Latent membrane protein 2 (LMP2), which is an important protein of Epstein-Barr virus (EBV) in the latent phase to mediate metastasis and recurrence, has shown great potential as a targeting antigen in mRNA vaccine for nasopharyngeal carcinoma (NPC) therapy. In this study, an LMP2 mRNA vaccine was developed based on a serum-resistant fluorinated polyethyleneimine (PF) with the self-adjuvant effect for achieving a strong anti-tumor immunity in NPC treatment. Specifically, the proposed vaccine PEG[PF/mLMP2] was comprised of a PF/mLMP2 core formed by the cationic PF and LMP2 mRNA, together with a dialdehyde poly (ethyl glycol) (OHC-PEG-CHO) coating.

Integrated Single-Cell and Spatial Transcriptome Reveal Metabolic Gene SLC16A3 as a Key Regulator of Immune Suppression in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers, usually diagnosed at an advanced stage. Metabolic reprogramming plays a significant role in HCC progression, probably related to immune evasion, yet the key gene is unclear. In this study, six metabolism-related genes with prognostic implications were screened.

Tumor burden quantified by Soluble B-Cell Maturation Antigen and Metabolic Tumor Volume determine myeloma CAR-T outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection.

Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children.

Background: B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common childhood cancer. Despite a high overall cure rate, relapsed B-cell ALL remains a leading cause of cancer-related death among children. The addition of the bispecific T-cell engager molecule blinatumomab (an anti-CD19 and anti-CD3 single-chain molecule) to therapy for newly diagnosed standard-risk (as defined by the National Cancer Institute) B-cell ALL in children may improve outcomes.