Platform study of circulating tumor DNA directed adjuvant chemotherapy in colon cancer (CLAUDIA colon cancer, KCSG CO22-12).

Background: Tumor-informed circulating tumor DNA (ctDNA) analysis allows for the sensitive detection of minimal residual disease (MRD) and has the potential to enhance patient stratification for adjuvant chemotherapy. We hypothesize that intensifying adjuvant chemotherapy in colon cancer patients with postoperative MRD positivity may reduce recurrence and improve survival outcomes.

Methods: This multi-center platform trial (NCT05534087) consists of a prospective observational study (Part 1) and an interventional randomized trial (Part 2).

Multiplex analysis of colorectal cancer tissue describes the composition, cell biology and spatial effects of cell-in-cell events and identifies a T cell-dependent prognostic signature.

Cell-in-cell (CIC) structures, in which one cell is entirely engulfed by another, have been associated with poor outcomes in cancers. However, the mechanisms underlying this association remain poorly understood. We performed multiplex imaging of 56 cell identity, cell 'state' and cancer 'hallmark' proteins to characterise CICs, map their spatial interactions, and assess clinical associations across 444 tumour cores from 148 colorectal cancer patients, which contained over one million spatially resolved cells.

High-Resolution Spatial Proteomics Characterises Colorectal Cancer Consensus Molecular Subtypes.

Background: Identification of the consensus molecular subtypes (CMS) opened significant potential for understanding the tumor biology and intertumoral heterogeneity of colorectal cancer (CRC). However, molecular subtyping in CRC traditionally relies on bulk transcriptomics, therefore, lacks spatial and single-cell level aspect.

Methods: We constructed tissue microarrays using tumor cores from 222 CRC patients.

ITGAV Regulation of LGALS3BP-JUNB Axis Facilitates the Cell-to-Cell Adhesion and Invasiveness of Hepatic Cancer Cells.

Background/aim: is a key regulator of hepatocellular carcinoma (HCC) progression, that promotes cell adhesion, migration, and activation. However, its transcriptional regulation remains poorly understood. This study aimed to elucidate the role of , a secreted regulator of the signaling pathway, in expression and its functional implications in tumor progression.

FGFR4 promotes CAF activation through the CXCL10-CXCR3 axis in colon cancer.

Cancer-associated fibroblasts (CAFs) promote the malignant phenotype of cancer through crosstalk with tumor and immune cells within the tumor microenvironment. Therefore, the mechanisms underlying CAF activation require in-depth study to develop strategies targeting CAFs during cancer immunotherapy. In this study, we investigated the role of FGFR4 in CAF regulation in colon cancer.

Long-term Immunogenicity of the 13-valent Pneumococcal Conjugate Vaccine during Adjuvant Chemotherapy in Patients with Gastric and Colorectal Cancer: A 5-year Follow-up of a Randomized Controlled Trial.

Purpose: Current guidelines recommend vaccination at least two weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response.

Integrated multiplex analysis of cell death regulators in stage II colorectal cancer suggests patients with 'persister' cell profiles fail to benefit from adjuvant chemotherapy.

Objective: Inducing tumour cell apoptosis is a primary objective of chemotherapy but, to date, there are no validated biomarkers of apoptosis sensitivity or resistance. Our objective was to image multiple apoptosis pathway proteins at single cell level and determine multi-protein associations with recurrence risk and chemotherapy response in patients with stage II colorectal cancer (CRC).

Methods And Analysis: Multiplexed imaging of 16 proteins in the intrinsic and extrinsic apoptosis pathways at single cell resolution on resected tissue from 194 patients with stage II CRC who either received adjuvant chemotherapy (n108) or were treated with surgery only (n=86).

as a Prognostic Biomarker: Linking Copy Number Variation to EMT and Survival in Colon Cancer.

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles.

Inhibitory Effects of Decursin Derivative against Lipopolysaccharide-Induced Inflammation.

Background: This study aims to explore the protective role of JB-V-60-a novel synthetic derivative of decur-sin-against lipopolysaccharide (LPS)-induced inflammation.

Methods: We examined the effects of JB-V-60 on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human pulmonary artery endothelial cells (HPAECs). Additionally, we assessed its effects on iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in LPS-exposed mice.

Tumor Immune Microenvironment Biomarkers for Recurrence Prediction in Locally Advanced Rectal Cancer Patients after Neoadjuvant Chemoradiotherapy.

Background/objectives: The tumor microenvironment (TME) has emerged as a significant prognostic factor. This study aimed to identify prognostic factors by combining clinicopathologic parameters and the TME biomarkers in patients who underwent surgery following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC).

Methods: CD8 T cells, CXCR3, CXCL10, and α-smooth muscle actin (α-SMA) were analyzed via immunohistochemical staining.

Spatial effects of infiltrating T cells on neighbouring cancer cells and prognosis in stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single-cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil (5FU)-based chemotherapy.

Galectin 3-binding protein (LGALS3BP) depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1 (TGF-β1) availability and inhibits hepatocarcinogenesis.

Background: Increased Galectin 3-binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.

Methods: The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and HCC.

The beneficial effects of lupeol on particulate matter-mediated pulmonary inflammation.

Particulate matter (PM) poses significant health risks, especially fine particles (PM) that can cause severe lung injuries. Lupeol, a phytosterol from medicinal plants, has potential anti-cancer properties. This study investigated lupeol's protective effects against PM-induced lung damage.

Holistic evaluation of a machine learning-based timing calibration for PET detectors under varying data sparsity.

Modern PET scanners offer precise TOF information, improving the SNR of the reconstructed images. Timing calibrations are performed to reduce the worsening effects of the system components and provide valuable TOF information. Traditional calibration procedures often provide static or linear corrections, with the drawback that higher-order skews or event-to-event corrections are not addressed.

Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience.

The role of induction chemotherapy (IC) in locally advanced oropharyngeal cancer (OPC) remains debatable, and suitable candidates for de-escalation treatment in these patients have not been fully identified. Therefore, the present study aimed to identify high-risk candidates for human papillomavirus (HPV)-positive OPC by analyzing patients who underwent IC followed by chemoradiotherapy (CRT) to guide optimal treatment strategies. Patients diagnosed with stage III-IVA OPC and treated with a minimum of two cycles of IC followed by CRT, between 2004 and 2020, were retrospectively reviewed.

Temozolomide promotes matrix metalloproteinase 9 expression through p38 MAPK and JNK pathways in glioblastoma cells.

Glioblastoma (GBM) is a highly aggressive and deadly brain cancer. Temozolomide (TMZ) is the standard chemotherapeutic agent for GBM, but the majority of patients experience recurrence and invasion of tumor cells. We investigated whether TMZ treatment of GBM cells regulates matrix metalloproteinases (MMPs), which have the main function to promote tumor cell invasion.

AZGP1 deficiency promotes angiogenesis in prostate cancer.

Background: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive.

Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1), a protein with important functions, has been recognized as a potential therapeutic target for the treatment of sepsis. One possible mechanism for this is that inhibiting HMGB1 secretion can exert antiseptic effects, which can restore the integrity of the vascular barrier. (7S)-(+)-cyclopentyl carbamic acid 8,8-dimethyl-2-oxo-6,7-dihydro-2H,8H-pyrano[3,2-g]chromen-7-yl-ester (CGK012) is a newly synthesized pyranocoumarin compound that could function as a novel small-molecule inhibitor of the Wnt/β-catenin signaling pathway.

Therapeutic effects of hederacolchiside A1 on particulate matter-induced pulmonary injury.

Particulate matter (PM) comprises a hazardous mixture of inorganic and organic particles that carry health risks. Inhaling fine PM particles with a diameter of ≤2.5 μm (PM) can promote significant lung damage.

Spatial Effects of Infiltrating T cells on Neighbouring Cancer Cells and Prognosis in Stage III CRC patients.

Colorectal cancer (CRC) is one of the most frequently occurring cancers, but prognostic biomarkers identifying patients at risk of recurrence are still lacking. In this study, we aimed to investigate in more detail the spatial relationship between intratumoural T cells, cancer cells, and cancer cell hallmarks, as prognostic biomarkers in stage III colorectal cancer patients. We conducted multiplexed imaging of 56 protein markers at single cell resolution on resected fixed tissue from stage III CRC patients who received adjuvant 5-fluorouracil-based chemotherapy.

Deep learning-based automated pipeline for blood vessel detection and distribution analysis in multiplexed prostate cancer images.

Prostate cancer is a highly heterogeneous disease, presenting varying levels of aggressiveness and response to treatment. Angiogenesis is one of the hallmarks of cancer, providing oxygen and nutrient supply to tumors. Micro vessel density has previously been correlated with higher Gleason score and poor prognosis.

Comparative Study on the Immunogenicity of COVID-19 mRNA Vaccines in Patients Receiving Adjuvant and Palliative Chemotherapy.

This study was conducted to investigate potential differences in vaccine efficacy between patients undergoing palliative chemotherapy and receiving adjuvant chemotherapy. Additionally, the study proved the influence of vaccination timing on vaccine efficacy during active chemotherapy. Anti-receptor-binding domain (RBD) IgG binding antibody assays and surrogate neutralizing antibody assays were performed after BNT162b2 or mRNA-1273 vaccination in 45 solid cancer patients (23 adjuvant and 22 palliative chemotherapy) and in 24 healthy controls before vaccination (baseline), at every two to four weeks after the first (post-dose 1) and the second vaccination (post-dose 2).

The Therapeutic Potential of (+)-Afzelechin for Alleviating Sepsis-Associated Pulmonary Injury.

Sepsis-induced acute lung injury (ALI) poses a common and formidable challenge in clinical practice, currently lacking efficacious therapeutic approaches. This study delves into the evaluation of (+)-afzelechin (AZC), a natural compound derived from with a diverse array of properties, encompassing antioxidant, anticancer, antimicrobial, and cardiovascular effects to ascertain its effectiveness and underlying mechanisms in mitigating sepsis-induced ALI through animal experimentation. An ALI mouse model induced by sepsis was established through lipopolysaccharide (LPS) administration, and various analytical techniques, including quantitative real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay were employed to gauge inflammatory cytokine levels, lung injury, and associated signaling pathways.

Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury.

Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 μm (PM) can lead to significant lung impairments.

3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging.

Mapping the human body at single cell resolution in three dimensions (3D) is important for understanding cellular interactions in context of tissue and organ organization. 2D spatial cell analysis in a single tissue section may be limited by cell numbers and histology. Here we show a workflow for 3D reconstruction of multiplexed sequential tissue sections: MATRICS-A (Multiplexed Image Three-D Reconstruction and Integrated Cell Spatial - Analysis).