Spatial dissection of tumour microenvironments in gastric cancers reveals the immunosuppressive crosstalk between fibroblasts and -activated macrophages.

Background: A spatially resolved, niche-level analysis of tumour microenvironments (TME) can provide insights into cellular interactions and their functional impacts in gastric cancers (GC).

Objective: Our goal was to translate the spatial organisation of GC ecosystems into a functional landscape of cellular interactions involving malignant, stromal and immune cells.

Design: We performed spatial transcriptomics on nine primary GC samples using the Visium platform to delineate the transcriptional landscape and dynamics of malignant, stromal and immune cells within the GC tissue architecture, highlighting cellular crosstalks and their functional consequences in the TME.

Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1.

Background: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression.

Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts.

Background: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC.

Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer.

Aims: Immunotherapy has shown remarkable effects on several malignancies; however, its impact on gastric cancers has been limited. Therefore, a novel strategy to overcome resistance to immunotherapy is required. In this study, we compared the gene expression profiles of two murine GC cell lines that exhibited different effects on tumor immunity.

Secretome analysis reveals reduced expression of COL4A2 in hypoxic cancer-associated fibroblasts with a tumor-promoting function in gastric cancer.

Background: Cancer-associated fibroblasts (CAFs) are major components of the tumor microenvironment (TME). Hypoxic TME is known to promote tumor progression. However, how a hypoxic condition regulates CAFs remains elusive.

Curcumin inhibits the cancer‑associated fibroblast‑derived chemoresistance of gastric cancer through the suppression of the JAK/STAT3 signaling pathway.

The present study aimed to investigate whether the Janus‑activated kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is a critical mechanism underlying the cancer‑associated fibroblast (CAF)‑induced chemoresistance of gastric cancer (GC). In addition, the present study tried to suggest a natural product to compromise the effects of CAF on the chemoresistance of GC. The results of cell proliferation assay revealed that the conditioned medium (CM) collected from CAFs further increased resistance to 5‑fluorouracil (5‑FU) in GC cell lines.

Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer.

Purpose: Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.

Spatially Distinct Reprogramming of the Tumor Microenvironment Based On Tumor Invasion in Diffuse-Type Gastric Cancers.

Purpose: Histologic features of diffuse-type gastric cancer indicate that the tumor microenvironment (TME) may substantially impact tumor invasiveness. However, cellular components and molecular features associated with cancer invasiveness in the TME of diffuse-type gastric cancers are poorly understood.

Experimental Design: We performed single-cell RNA-sequencing (scRNA-seq) using tissue samples from superficial and deep invasive layers of cancerous and paired normal tissues freshly harvested from five patients with diffuse-type gastric cancer.

Cancer-Associated Fibroblast-Induced Resistance to Chemotherapy and Radiotherapy in Gastrointestinal Cancers.

In the past few decades, the role of cancer-associated fibroblasts (CAFs) in resistance to therapies for gastrointestinal (GI) cancers has emerged. Clinical studies focusing on GI cancers have revealed that the high expression of CAF-related molecules within tumors is significantly correlated with unfavorable therapeutic outcomes; however, the exact mechanisms whereby CAFs enhance resistance to chemotherapy and radiotherapy in GI cancers remain unclear. The cells of origin of CAFs in GI cancers include normal resident fibroblasts, mesenchymal stem cells, endothelial cells, pericytes, and even epithelial cells.

Vasorelaxant effects of 50 commonly used traditional herbal prescriptions on isolated rat aortic rings.

Objective: To investigate the vasorelaxant activities of 50 common traditional herbal prescriptions (THPs) on isolated rat aortic rings.

Methods: An electric extractor was used to extract THPs. Rat aortic rings were precontracted using phenylephrine in organ chambers containing Krebs-Henseleit solution.

Inhibiting the GAS6/AXL axis suppresses tumor progression by blocking the interaction between cancer-associated fibroblasts and cancer cells in gastric carcinoma.

Background: The effects of cancer-associated fibroblasts (CAF) on the progression of gastric carcinoma (GC) has recently been demonstrated. However, agents targeting the interaction between CAF and GC cells have not been applied in a clinical setting. Here, we examined if inhibition for Axl receptor tyrosine kinase (AXL) can suppress CAF-induced aggressive phenotype in GC.

Scaffold-Assisted Ectopic Transplantation of Internal Organs and Patient-Derived Tumors.

Xenotransplantation of human tissues into immunodeficient mice has emerged as an invaluable preclinical model to study human biology and disease progression and predict clinical response. The most common anatomical site for tissue transplantation is the subcutaneous pocket due to simple surgical procedures and accessibility for gross monitoring and advanced imaging modalities. However, subcutaneously implanted tissues initially experience a sharp change in oxygen and nutrient supply and increased mechanical deformation.

Vasorelaxant Effect of (Siebold) Siebold & Zucc. Branch through the Endothelium-Dependent Pathway.

Korean plum ( (Siebold) Siebold & Zucc.) has long been used as a health food or herbal medicine in Asia. Previous studies have shown that several plants of the genus have vasodilatory and antihypertensive effects; we hypothesized that branches may have a vasorelaxant effect.

Endothelium-Dependent Vasorelaxant Effect of Branch on Isolated Rat Thoracic Aorta.

Peach ( (L.) Batsch) is a popular fruit consumed by people worldwide, owing to its pleasant flavor and high mineral nutrient content. A few plants from the genus , such as , , and have shown vasorelaxant and vasodilatory effects, to date, no study has investigated the vasorelaxation effects of the branch extract (PPE).

Role of Cancer-Associated Fibroblast in Gastric Cancer Progression and Resistance to Treatments.

Although the survival of gastric cancer (GC) patients has gradually improved, the outcomes of advanced GC patients remain unsatisfactory despite standard treatment with conventional chemotherapy or targeted agents. Several studies have shown that cancer-associated fibroblasts (CAFs), a major component of tumor stroma in GC, may have significant roles in GC progression and resistance to treatments. CAFs are a major source of various secreted molecules in the tumor microenvironment, which stimulate cancer cells and other noncancerous components of GC.

Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer.

Background: Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC.

Methods: To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed.

Inhibition of Discoidin Domain Receptor 1 Prevents Stroma-Induced Peritoneal Metastasis in Gastric Carcinoma.

Discoidin domain receptor 1 (DDR1) is activated by fibrillar (triple-helical) collagens and collagen IV, which are major components of tumor stroma; thus, DDR1 might be a critical mediator of communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in gastric carcinoma. We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in gastric carcinoma tissues from a previously characterized and established gastric carcinoma patient cohort.

Experimental research of hypotensive and hypolipidemic effects with Modified Sanhuang Xiexin Decoction ().

Objective: To investigate the hypotensive and hypolipidemic effects of Modified Sanhuang Xiexin Decoction (, HVC1), a herbal prescription for the vascular diseases in Chinese medicine and evaluate the acute and subchronic oral toxicities.

Methods: Fifty-six spontaneous hypertensive rats (SHRs) were used to investigate the hypotensive and hypolipidemic effect of HVC1. Rats in the normal group (n=8) were fed with normal diet.

Vasorelaxant effects of Angelica decursiva root on isolated rat aortic rings.

Background: Hypertension is one of the most important risk factors for cardiovascular disease (CVD) and a worldwide problem. Despite increases in the development of synthetic drugs for hypertension treatment, the rate of untreated and uncontrolled hypertension remains high. These drugs are effective, but can also cause side effects.

AKT inhibition is an effective treatment strategy in ARID1A-deficient gastric cancer cells.

Background: The At-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancers (GCs) with a poor prognosis. Growing evidence indicates that loss of ARID1A expression leads to activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by AKT phosphorylation. We aim to investigate the different sensitivity for the AKT inhibitor in ARID1A-deficient GC cells.

HVC1 ameliorates hyperlipidemia and inflammation in LDLR mice.

Background: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects.

Methods: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR) mice fed a high-cholesterol diet for 13 weeks.

Wound Healing Effects of Matsumura Bark in Scalded Rats.

Pruni Cortex has been used to treat asthma, measles, cough, urticaria, pruritus, and dermatitis in traditional Korean medicine. The objective of this study was to investigate the effects of Matsumura bark methanol extract (PYE) on scald-induced dorsal skin wounds in rats. Scalds were produced in Sprague-Dawley rats with 100°C water and treated with 5% and 20% PYE (using Vaseline as a base), silver sulfadiazine (SSD), and Vaseline once a day for 21 days, beginning 24 hours after scald by treatment group allocation.

Discoidin domain receptor 1 activity drives an aggressive phenotype in gastric carcinoma.

Background: Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that utilizes collagen as a ligand, is a key molecule in the progression of solid tumors as it regulates the interaction of cancer cells with the tumor stroma. However, the clinical relevance of DDR1 expression in gastric carcinoma is yet to be investigated. Here, we assessed the role of DDR1 in mediating the aggressive phenotype of gastric carcinoma and its potential as a therapeutic target.

Preoperative serum levels of insulin-like growth factor-binding protein 2 predict prognosis of gastric cancer patients.

It has been reported that serum insulin-like growth factor-binding protein 2 (IGFBP2) levels are elevated in various types of cancers. However, the clinicopathologic and prognostic implications of circulating IGFBP2 have never been investigated in gastric cancer. We tested IGFBP2 levels in the sera of 118 gastric cancer patients and 34 healthy controls using enzyme-linked immunosorbent assay (ELISA).