Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

Integrin-activating protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets.

Matrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells [T. Sato , , 262-265 (2009); T. Sato , , 1762-1772 (2011)].

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

High-throughput drug screening identifies SMAC mimetics as enhancers of NK cell cytotoxicity in chronic myeloid leukemia.

Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma.

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2.

Comparative genomic analysis unveiling the mutational landscape associated with premalignant lesions and early-stage gastric cardia cancer.

This study enrolled 10 patients diagnosed with premalignant lesions and early-stage gastric cardia adenocarcinoma (GCA), confirmed through endoscopic examination. These patients were subjected to next-generation sequencing (NGS) using a customized 1123-gene panel to identify genetic alterations and signaling pathways. The results were compared to stage IIB to IV GCA samples from the cancer genome atlas (TCGA) and a cohort of Hong Kong patients.

Artificial Intelligence for Predicting HER2 Status of Gastric Cancer Based on Whole-Slide Histopathology Images: A Retrospective Multicenter Study.

Human epidermal growth factor receptor 2 (HER2) positive gastric cancer (GC) shows a robust response to the combined therapy based HER2-targeted therapy. The application of these therapies is highly dependent on the evaluation of tumor HER2 status. However, there are many risks and challenges in HER2 assessment in GC.

Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells.

The unfolded protein response (UPR) pathway is crucial for tumorigenesis, mainly by regulating cancer cell stress responses and survival. However, whether UPR factors facilitate cell-cell communication between cancer cells and immune cells to drive cancer progression remains unclear. We found that adenosine 3',5'-monophosphate response element-binding protein 3-like protein 2 (CREB3L2), a noncanonical UPR factor, is overexpressed and activated in triple-negative breast cancer, where its cleavage releases a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells.

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models.

Recent research has shown that mtDNA-deficient cancer cells (ρ cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1) mice markedly delayed tumor formation after grafting ρ cancer cells.

Establishing a living biobank of pediatric high-grade glioma and ependymoma suitable for cancer pharmacology.

Background: Brain tumors are the deadliest solid tumors in children and adolescents. Most of these tumors are glial in origin and exhibit strong heterogeneity, hampering the development of effective therapeutic strategies. In the past decades, patient-derived tumor organoids (PDT-O) have emerged as powerful tools for modeling tumoral cell diversity and dynamics, and they could then help defining new therapeutic options for pediatric brain tumors.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Coptisine inhibits esophageal carcinoma growth by modulating pyroptosis via inhibition of HGF/c-Met signaling.

Esophageal carcinoma is a highly prevalent malignancy worldwide. The present study aimed to investigate the mechanism by which the natural compound coptisine affects pyroptosis in esophageal squamous cell carcinoma (ESCC). The expression of c-Met in ESCC patients was assessed by immunohistochemical analysis of tissue microarrays.

Deep learning-based image domain reconstruction enhances image quality and pulmonary nodule detection in ultralow-dose CT with adaptive statistical iterative reconstruction-V.

Objectives: To evaluate the image quality and lung nodule detectability of ultralow-dose CT (ULDCT) with adaptive statistical iterative reconstruction-V (ASiR-V) post-processed using a deep learning image reconstruction (DLIR)-based image domain compared to low-dose CT (LDCT) and ULDCT without DLIR.

Materials And Methods: A total of 210 patients undergoing lung cancer screening underwent LDCT (mean ± SD, 0.81 ± 0.

mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs.

mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular dynamics simulations of mTOR oncogenic variants.

Novel Drug Delivery Particles Can Provide Dual Effects on Cancer "Theranostics" in Boron Neutron Capture Therapy.

Boron (B) neutron capture therapy (BNCT) is a novel non-invasive targeted cancer therapy based on the nuclear capture reaction B (n, alpha) Li that enables the death of cancer cells without damaging neighboring normal cells. However, the development of clinically approved boron drugs remains challenging. We have previously reported on self-forming nanoparticles for drug delivery consisting of a biodegradable polymer, namely, "AB-type" Lactosome nanoparticles (AB-Lac particles)- highly loaded with hydrophobic B compounds, namely -Carborane (Carb) or 1,2-dihexyl--Carborane (diC6-Carb), and the latter (diC6-Carb) especially showed the "molecular glue" effect.

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.

Inherited Thrombocytopenia Related Genes: GPS2 Mediates the Interplay Between ANKRD26 and ETV6.

Mutations in the genes , , and cause three clinically overlapping thrombocytopenias characterized by a predisposition to hematological neoplasms. The gene, which encodes a protein involved in protein-protein interactions, is downregulated by RUNX1 during megakaryopoiesis. Mutations in 5'UTR of ANKRD26, leading to ANKRD26-RT, disrupt this regulation, resulting in the persistent expression of ANKRD26, which leads to impaired platelet biogenesis and an increased risk of leukemia.

Genetic Characteristics of the Rat Fibroblast Cell Line Rat-1.

The Rat-1 cell line was established as a subclone of the parental rat fibroblastoid line F2408, derived from Fisher 344 rat embryos. Rat-1 cells are widely used in various research fields, especially in cancer biology, to study the effects of oncogenes on cell proliferation. They are also crucial for investigating signal transduction pathways and play a key role in drug testing and pharmacological studies due to their rapid proliferation.

Evolutionarily Developed Alternatively Spliced Exons Containing Translation Initiation Sites.

Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information.

Metabolomics-Driven Biomarker Discovery for Breast Cancer Prognosis and Diagnosis.

Breast cancer is a cancer with global prevalence and a surge in the number of cases with each passing year. With the advancement in science and technology, significant progress has been achieved in the prevention and treatment of breast cancer to make ends meet. The scientific intradisciplinary subject of "metabolomics" examines every metabolite found in a cell, tissue, system, or organism from different sources of samples.

The Effects of Social Feedback Through the "Like" Feature on Brain Activity: A Systematic Review.

Background: Problematic social media (SM) use is a growing concern, particularly among adolescents who are drawn to these platforms for social interactions important to their age group. SM dependence is characterized by excessive, uncontrolled usage that impairs personal, social, and professional aspects. Despite the ongoing debate over recognizing SM addiction as a distinct diagnostic category, the impact of social feedback, particularly through the "like" button, on brain activity remains under scrutiny.

Inhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.

Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.