Anticancer potentialsof chaga and notoginseng against dog bladder cancer organoids.

Muscle-invasive bladder cancer (MIBC) is a common form of BC in dogs. Adjuvant chemotherapy administration is commonly applied in MIBC cases, but patients sometimes experience treatment failure and recurrence. Therefore, supplements with anticancer properties, such as traditional Chinese medicines (TCMs), are required, and they have been widely used in Japanese human medicine and may be useful in veterinary medicine.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

In-vitro and in-vivo assessment of biocompatibility and efficacy of ostrich eggshell membrane combined with platelet-rich plasma in Achilles tendon regeneration.

Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role.

Unraveling the complexity of HRD assessment in ovarian cancer by combining genomic and functional approaches: translational analyses of MITO16-MaNGO-OV-2 trial.

Background: Ovarian cancer (OvC) constitutes significant management challenges primarily due to its late-stage diagnosis and the development of resistance to chemotherapy. The standard treatment regimen typically includes carboplatin and paclitaxel, with the addition of poly (ADP-ribose) polymerase inhibitors for patients with high-grade serous ovarian cancer (HGSOC) harboring BRCA1/2 mutations. However, the variability in treatment responses suggests the need to investigate factors beyond BRCA1/2 mutations, such as DNA repair mechanisms and epigenetic alterations.

Immune-related gene SOX10 affects ferroptosis in pancreatic cancer and facilitates tumor progression by targeting CMTM7-mediated Wnt/β-catenin signaling pathway.

Objectives: SOX10 is crucially implicated in various cancer, yet the regulatory role in pancreatic cancer (PC) remains enigmatic. Underlying molecular mechanisms of SOX10 in PC were explored in our study.

Methods: Relationships between SOX10 and immune landscape were estimated using bioinformatic approaches.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer.

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data.

Genomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines.

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines.

Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadth.

Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection.

Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.

Prognostic relevance of CD163 immune cells in patients with metastatic breast cancer.

Metastatic breast cancer (MBC) is generally considered an incurable disease and even though new treatments are available, the median survival is approximately three years. The introduction of immune therapies for MBC highlights the importance of the immune system in cancer progression and treatment. CD163 anti-inflammatory myeloid cells, including tumor associated macrophages (TAMs), are known to be of relevance in early breast cancer but their role in MBC is not yet established.

Utilizing Lateral Sprouting Axons to Reinnervate a Transferred Free Muscle to Enhance Distal Muscle Recovery When Performing High-Level Nerve Repair : Experimental Rat Study.

Background: High-level median or ulnar nerve injuries and repairs typically result in suboptimal re-innervation of distal muscles. Functioning Free Muscle Transplantation (FFMT) is increasingly recognized as an effective method to restore function in chronic muscle denervation cases. This study investigates the efficacy of using an additional FFMT, neurotized by lateral sprouting axons from a repaired high-level mixed nerve in the upper limb, to enhance distal hand function.

Hyperglycemia causes differential change in macrophage population in the lacrimal gland, conjunctiva and cornea.

Background: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population.

BRCA testing in metastatic castration-resistant prostate cancer: successes and troubles in a real world setting. An Italian Multicentric study.

Objective: Prostate cancer (PCa) is the most common cause of cancer-related deaths in men worldwide. BRCA1/2 genes are reported altered in approximately 1% and 8% of PCa cases, respectively. To date, formalin-fixed paraffin-embedded (FFPE) tissues have a consolidate use in the clinical practice, but with a significant drawback related to DNA/RNA degradation during the pre-analytical process.

Intratumor heterogeneity of EGFR expression mediates targeted therapy resistance and formation of drug tolerant microenvironment.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used to treat non-small cell lung cancers with EGFR mutations, but drug resistance often emerges. Intratumor heterogeneity is a known cause of targeted therapy resistance and is considered a major factor in treatment failure. This study identifies clones of EGFR-mutant non-small cell lung tumors expressing low levels of both wild-type and mutant EGFR protein.

STAT1 regulates immune-mediated intestinal stem cell proliferation and epithelial regeneration.

The role of the immune system in regulating tissue stem cells remains poorly understood, as does the relationship between immune-mediated tissue damage and regeneration. Graft vs. host disease (GVHD) occurring after allogeneic bone marrow transplantation (allo-BMT) involves immune-mediated damage to the intestinal epithelium and its stem cell compartment.

Machine Learning identifies remodeling patterns in human lung extracellular matrix.

Organ function depends on the three-dimensional integrity of the extracellular matrix (ECM). The structure resulting from the location and association of ECM components is a central regulator of cell behavior, but a dearth of matrix-specific analysis keeps it unresolved. Here, we deploy a high-resolution, 3D ECM mapping method and design a machine-learning powered pipeline to detect and characterize ECM architecture during health and disease.

Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14, a rare rs5361 in SELE, and a common rs1050462 in HLA-B.

Anti-PD1 therapies induce an early expansion of Ki67CD8 T cells in metastatic non-oncogene addicted NSCLC patients.

Pembrolizumab (an anti-PD1 antibody) alone or combined with chemotherapy represented the standard of care for advanced non-oncogene addicted non-small cell lung cancer (NSCLC) patients. These therapies induced early modifications of the immune response impacting the clinical outcome. Identifying early changes in the immune system was critical to directing the therapeutic choice and improving the clinical outcome.

Prolonged fecal shedding of replication-competent virus, lasting immune activation, and intestinal inflammation in a rhesus macaque after experimental SARS-CoV-2 infection.

Infection of an adult rhesus macaque with SARS-CoV-2 led to viral RNAemia in nose, throat, and lungs. The animal also presented extended fecal shedding of viral genomic and subgenomic messenger RNA and replication-competent virus for more than 3 weeks after infection. Positron emission tomography revealed increased intestinal glucose metabolism which was histologically related to inflammation of the ileum.

First report of hop stunt viroid infecting luffa and cantaloupe in Taiwan.

Luffa (Luffa cylindrica (L.) M. Roem.