A novel case of glial transdifferentiation in renal medullary carcinoma brain metastasis.

Renal medullary carcinoma is a rare undifferentiated tumor of the kidney associated with sickle cell trait and characterized by INI1 (SMARCB1) loss. Although metastasis to lungs, lymph nodes, and bone is commonly reported, distant spread to the central nervous system almost never occurs. Here we present an unusual case of a patient with renal medullary carcinoma with metastasis to the brain following treatment which included tazemetostat, an EZH2 inhibitor.

Comprehensive analysis of H3K27me3 LOCKs under different DNA methylation contexts reveal epigenetic redistribution in tumorigenesis.

Background: Histone modification H3K27me3 plays a critical role in normal development and is associated with various diseases, including cancer. This modification forms large chromatin domains, known as Large Organized Chromatin Lysine Domains (LOCKs), which span several hundred kilobases.

Result: In this study, we identify and categorize H3K27me3 LOCKs in 109 normal human samples, distinguishing between long and short LOCKs.

Modulation of DAPK1 expression by its alternative splice variant DAPK1-215 in cancer.

Background: Death-Associated Protein Kinase 1 (DAPK1) family members are calcium/calmodulin-regulated serine/threonine kinases implicated in cell death, normal development, and human diseases. However, the regulation of DAPK1 expression in cancer remains unclear.

Methods: We examined the expression and functional impact of a DAPK1 splice variant, DAPK1-215, in multiple cancer cell lines.

Dual role of Cathepsin S in cutaneous melanoma: insights from mendelian randomization and bioinformatics analysis.

Background: Cutaneous melanoma (CM) is strongly associated with ultraviolet (UV) radiation, which contributes to the transformation of melanocytes into melanoma by inducing specific DNA damage. Here, we investigated the causal relationship between CM and genes related to sun-damaged skin, exploring specific target genes through various bioinformatics analyses.

Methods: The Gene Expression Omnibus (GEO) database was used to obtain differential genes for CM and normal skin, and the Genome-Wide Association Studies (GWAS) analysis offered summary-level melanoma data for CM.

Study protocol: multi-centre, randomised controlled clinical trial exploring stromal targeting in locally advanced pancreatic cancer; STARPAC2.

Background: Pancreatic cancer (PDAC: pancreatic ductal adenocarcinoma, the commonest form), a lethal disease, is best treated with surgical excision but is feasible in less than a fifth of patients. Around a third of patients presentlocally advanced, inoperable, non-metastatic (laPDAC), whose stadrd of care is palliative chemotherapy; a small minority are down-sized sufficiently to enable surgical excision. We propose a phase II clinical trial to test whether a combination of standard chemotherapy (gemcitabine & nab-Paclitaxel: GEM-NABP) and repurposing All Trans Retinoic Acid (ATRA) to target the stroma may extend progression-free survival and enable successful surgical resection for patients with laPDAC, since data from phase IB clinical trial demonstrate safety of GEM-NABP-ATRA combination to patients with advanced PDAC with potential therapeutic benefit.

Benchmarking cell type annotation methods for 10x Xenium spatial transcriptomics data.

Background: Imaging-based spatial transcriptomics technologies allow us to explore spatial gene expression profiles at the cellular level. Cell type annotation of imaging-based spatial data is challenging due to the small gene panel, but it is a crucial step for downstream analyses. Many good reference-based cell type annotation tools have been developed for single-cell RNA sequencing and sequencing-based spatial transcriptomics data.

Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation.

Increased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines.

Variants and vaccines impact nasal immunity over three waves of SARS-CoV-2.

Viral variant and host vaccination status impact infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet how these factors shift cellular responses in the human nasal mucosa remains uncharacterized. We performed single-cell RNA sequencing (scRNA-seq) on nasopharyngeal swabs from vaccinated and unvaccinated adults with acute Delta and Omicron SARS-CoV-2 infections and integrated with data from acute infections with ancestral SARS-CoV-2. Patients with Delta and Omicron exhibited greater similarity in nasal cell composition driven by myeloid, T cell and SARS-CoV-2 cell subsets, which was distinct from that of ancestral cases.

UDA-seq: universal droplet microfluidics-based combinatorial indexing for massive-scale multimodal single-cell sequencing.

The use of single-cell combinatorial indexing sequencing via droplet microfluidics presents an attractive approach for balancing cost, scalability, robustness and accessibility. However, existing methods often require tailored protocols for individual modalities, limiting their automation potential and clinical applicability. To address this, we introduce UDA-seq, a universal workflow that integrates a post-indexing step to enhance throughput and systematically adapt existing droplet-based single-cell multimodal methods.

BRAT1 - a new therapeutic target for glioblastoma.

Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.

Single-cell RNA sequencing of the carotid artery and femoral artery of rats exposed to hindlimb unloading.

Background: Prolonged spaceflight is known to cause vascular deconditioning and remodeling. Tail suspension, a widely used spaceflight analog, is reported to result in vascular remodeling of rats. However, little is known about the cellular atlas of the heterogeneous cells of CA and FA from hindlimb-unloaded rats.

Metabolic interplays between the tumour and the host shape the tumour macroenvironment.

Metabolic reprogramming of cancer cells and the tumour microenvironment are pivotal characteristics of cancers, and studying these processes offer insights and avenues for cancer diagnostics and therapeutics. Recent advancements have underscored the impact of host systemic features, termed macroenvironment, on facilitating cancer progression. During tumorigenesis, these inherent features of the host, such as germline genetics, immune profile and the metabolic status, influence how the body responds to cancer.

Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC-MS/MS peptidome analysis.

Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelial cells, with a high rate of recurrence following surgical resection. Recurrence is categorized as early linked to aggressive tumor biology than late recurrence. This study aimed to identify novel peptide mass fingerprints (PMFs) and potential biomarker panels in the serum of CCA patients with early and late recurrence using mass spectrometry.

Investigation of Scutellaria Barbata's immunological mechanism against thyroid cancer using network pharmacology and experimental validation.

Thyroid cancer (TC) is the most common endocrine malignancy, with a rapidly increasing global incidence. Scutellariae Barbatae Herba (SBH) exhibits significant antitumor activity; however, its mechanism against TC remains unclear. This study aims to explore the immunotherapeutic mechanism of SBH in treating TC through network pharmacology, bioinformatics analysis, and experimental validation.

Epigenetic regulation of HOXA2 expression affects tumor progression and predicts breast cancer patient survival.

Accumulating evidence suggests that genetic and epigenetic biomarkers hold potential for enhancing the early detection and monitoring of breast cancer (BC). Epigenetic alterations of the Homeobox A2 (HOXA2) gene have recently garnered significant attention in the clinical management of various malignancies. However, the precise role of HOXA2 in breast tumorigenesis has remained elusive.

Convolutional neural networks for accurate real-time diagnosis of oral epithelial dysplasia and oral squamous cell carcinoma using high-resolution in vivo confocal microscopy.

Oral cancer detection is based on biopsy histopathology, however with digital microscopy imaging technology there is real potential for rapid multi-site imaging and simultaneous diagnostic analysis. Fifty-nine patients with oral mucosal abnormalities were imaged in vivo with a confocal laser endomicroscope using the contrast agents acriflavine and fluorescein for the detection of oral epithelial dysplasia and oral cancer. To analyse the 9168 images frames obtained, three tandem applied pre-trained Inception-V3 convolutional neural network (CNN) models were developed using transfer learning in the PyTorch framework.

Circulating tumour DNA in early stage and locally advanced NSCLC: ready for clinical implementation?

Circulating tumour DNA (ctDNA) can be released by cancer cells into biological fluids through apoptosis, necrosis or active release. In patients with non-small-cell lung cancer (NSCLC), ctDNA levels correlate with clinical and pathological factors, including histology, tumour size and proliferative status. Currently, ctDNA analysis is recommended for molecular profiling in patients with advanced-stage NSCLC.

Plasma S100A8/A9 level predicts response to immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.

Blood-based predictive markers for the efficacy of immune checkpoint inhibitors (ICIs) have not yet been established. We investigated the association of the plasma level of S100A8/A9 with the efficacy of immunotherapy. We evaluated patients with unresectable stage III/IV or recurrent non-small cell lung cancer (NSCLC) who were treated with ICIs at Okayama University Hospital.

Differential effects of β-hydroxybutyrate and α-ketoglutarate on HCT-116 colorectal cancer cell viability under normoxic and hypoxic low-glucose conditions: exploring the role of SRC, HIF1α, ACAT1, and SIRT2 genes.

Recent therapeutic strategies have highlighted the potential of β-hydroxybutyrate (BHB) and α-ketoglutarate (α-KG) as effective anticancer agents, particularly for colon cancer. These metabolites can modulate cellular metabolism and induce epigenetic changes, inhibiting tumor growth. Nonetheless, certain cancer cells may utilize ketone bodies, like BHB as nutrient sources under hypoxic conditions, potentially reducing treatment efficacy.

Kindlin-1 promotes gastric cancer cell motility through the Wnt/β-catenin signaling pathway.

Despite advances in gastric cancer diagnosis and treatment, its prognosis remains poor owing to aggressive tumor progression and metastasis. As understanding the relevant molecular mechanisms is essential to effectively improve patient outcomes, we elucidated the role of Kindlin-1 in gastric cancer progression and metastasis. Kindlin-1 expression was analyzed in 359 gastric cancer tissue samples provided by Kangnam Sacred Heart Hospital and publicly available GSE datasets.

Identifying a non-conserved site for achieving allosteric covalent inhibition of CECR2.

The bromodomain (BRD) represents a highly conserved structural module that provides BRD proteins with fundamental functionality in modulating protein-protein interactions involved in diverse biological processes such as chromatin-mediated gene transcription, DNA recombination, replication and repair. Consequently, dysregulation of BRD proteins has been implicated in the pathogenesis of numerous human diseases. In recent years, considerable scientific endeavors have focused on unraveling the molecular mechanisms underlying BRDs and developing inhibitors that target these domains.

Palmitoylation-dependent regulation of GPX4 suppresses ferroptosis.

S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator of ferroptosis, is reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 and increases its protein stability.

A dual role of Cohesin in DNA DSB repair.

Cells undergo tens of thousands of DNA-damaging events each day. Defects in repairing double-stranded breaks (DSBs) can lead to genomic instability, contributing to cancer, genetic disorders, immunological diseases, and developmental defects. Cohesin, a multi-subunit protein complex, plays a crucial role in both chromosome organization and DNA repair by creating architectural loops through chromatin extrusion.

Sleeve gastrectomy reveals the plasticity of the human gastric epithelium.

Gastrin is secreted following a rise in gastric pH, leading to gastric acid secretion. Sleeve gastrectomy (SG), a bariatric surgery where 80% of the gastric corpus is excised, presents a challenge for gastric pH homeostasis. Using histology, and single-cell RNA sequencing of the gastric epithelium in 12 women, we observed that SG is associated with an increase in a sub-population of acid-secreting parietal cells that overexpress respiratory enzymes and an increase in histamine-secreting enterochromaffin-like cells (ECLs).