The Interplay of TGF-β1 and Cholesterol Orchestrating Hepatocyte Cell Fate, EMT, and Signals for HSC Activation.

Background & Aims: Transforming growth factor-β1 (TGF-β1) plays important roles in chronic liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD involves various biological processes including dysfunctional cholesterol metabolism and contributes to progression to metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. However, the reciprocal regulation of TGF-β1 signaling and cholesterol metabolism in MASLD is yet unknown.

An aging and p53 related marker: promoter methylation negatively correlates with mRNA and protein expression in old age.

The process of aging has been associated with differential patterns of DNA methylation which relate to changes in gene expression. Hence, we aimed to identify genes with significant age-related methylation differences and to study their mRNA and protein expression profile. Genome-wide DNA methylation analysis was performed with the Illumina Infinium Methylation EPIC BeadChip Microarray on bisulfite-converted DNA prepared from monocytes derived from young (average age: 23.

MicroRNA-496 and Mechanistic Target of Rapamycin Expression are Associated with Type 2 Diabetes Mellitus and Obesity in Elderly People.

Background: Mechanistic target of rapamycin (mTOR) regulates lipid and glucose metabolism thus playing a key role in metabolic diseases like type 2 diabetes mellitus (T2DM). Recently, we demonstrated a functional interaction of microRNA-496 (miR-496) with mTOR and its impact on the regulation of human ageing.

Objectives: As T2DM is most prevalent in older adults, we hypothesized that miR-496 may also have an impact on mTOR regulation in T2DM.

Cytokine-mediated modulation of the hepatic miRNome: miR-146b-5p is an IL-6-inducible miRNA with multiple targets.

Interleukin-6 (IL-6)-type cytokines play important roles in liver (patho-)biology. For instance, they regulate the acute phase response to inflammatory signals and are involved in hepatocarcinogenesis. Much is known about the regulation of protein-coding genes by cytokines whereas their effects on the miRNome is less well understood.

Text mining, a race against time? An attempt to quantify possible variations in text corpora of medical publications throughout the years.

Background: The continuous growth of medical sciences literature indicates the need for automated text analysis. Scientific writing which is neither unitary, transcending social situation nor defined by a timeless idea is subject to constant change as it develops in response to evolving knowledge, aims at different goals, and embodies different assumptions about nature and communication. The objective of this study was to evaluate whether publication dates should be considered when performing text mining.

microRNA-496 - A new, potentially aging-relevant regulator of mTOR.

Recent findings strongly support a role for small regulatory RNAs in the regulation of human lifespan yet little information exists about the precise underlying mechanisms. Although extensive studies on model organisms have indicated that reduced activity of the nutrient response pathway, for example as a result of dietary restriction, can extend lifespan through the suppression of the protein kinase mechanistic target of rapamycin (mTOR), it still is subject of debate whether this mechanism is operative in humans as well. Here, we present findings indicating that human microRNA (miR)-496 targets 2 sites within the human mTOR 3'UTR.

CXCL12/CXCR4 display an inverse mRNA expression profile in gastric carcinoma that correlates with tumor progression.

Chemokines and their receptors have been shown to contribute to tumor growth and metastatic spread in various gastrointestinal cancer entities. In the present study, the mRNA expression profiles and clinical significance of chemokine ligand CXCL12 and its corresponding receptor CXCR4 were investigated in patients with gastric cancer (GC). Using quantitative polymerase chain reaction, the expression profile of CXCL12/CXCR4 was analyzed in resection specimens from the patients with GC (n=66) and in corresponding normal gastric tissues.

Chemokine/chemokine receptor pair CCL20/CCR6 in human colorectal malignancy: An overview.

Chemokines belong to a superfamily of small, cytokine-like proteins, which induce multiple physiological functions, particularly cytoskeletal rearrangement and compartment-specific migration through their interaction with G-protein-coupled receptors. Chemokines and their receptors have been widely acknowledged as essential and selective mediators in leukocyte migration in inflammatory response. It is now established that the chemokine/chemokine receptor system is also used by cancer cells to direct lymphatic and haematogenous spreading and additionally has an impact on the site of metastatic growth of different tumours.

Proangiogenic potency of MUC18 in arteriosclerotic disease.

Aim: Stenotic peripheral and dilatative arteriosclerotic diseases have different pathomechanism although associations between both diseases are well known. The adhesion molecule MUC18 is a cell membrane glycoprotein also known as the melanoma cell adhesion molecule. As MUC18 has proangiogenic potency in melanoma and prostate cancer this study investigated the role of MUC18 in patients with stenotic or dilatative arteriosclerotic disease as a putative biochemical marker.

MicroRNA target prediction: theory and practice.

The present study is one of the few that includes tissue samples in the evaluation of target prediction algorithms designed to detect microRNA (miRNA) sequences that might interact with particular messenger RNA (mRNA) sequences. Twelve different target prediction tools were used to find miRNA sequences that might interact with CCL20 gene expression. Different algorithms predicted controversial miRNA sequences for CCL20 regulation due to a different weighting of parameters.

Chemokine receptor CCR6 expression is regulated by miR-518a-5p in colorectal cancer cells.

Background: Recently, involvement of the chemokine/receptor system CCL20/CCR6 in colorectal cancer (CRC) progression was shown. Here, we analyzed the functional interaction of miRNA-518-5p (miR-518a-5p) with CCR6 and its impact on CCR6 expression in CRC cells.

Methods: MiR-518a-5p was identified by computer software to potentially interact with CCR6.

miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: significance of their regulation.

Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization.

CCR6/CCL20 chemokine expression profile in distinct colorectal malignancies.

Originally, chemokines and their G-protein-coupled receptors were described to regulate multiple physiological functions, particularly tissue architecture and compartment-specific migration of white blood cells. Now, it is established that the chemokine/chemokine receptor system is also used by cancer cells for migration and metastatic spread. Here, we examined the relative levels of CC-chemokine CCL20 and its corresponding receptor CCR6 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as in colorectal liver metastases (CRLM).

miR-21 functionally interacts with the 3'UTR of chemokine CCL20 and down-regulates CCL20 expression in miR-21 transfected colorectal cancer cells.

As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to demonstrate that miR-21 functionally interacts with the 3'UTR of CCL20 mRNA and down-regulates CCL20 in miR-21 mimic transfected CRC cell lines (Caco-2, SW480 and SW620). Thus, regulation of CCL20 expression by miR-21 might be a regulatory mechanism involved in progression of CRC.

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy.

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases.

Aim: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients.

Methods: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage IV CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29).

Results: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively.

CXC receptor-4 mRNA silencing abrogates CXCL12-induced migration of colorectal cancer cells.

Background: Interactions between CXCR4 and its ligand CXCL12 have been shown to be involved in cancer progression in colorectal cancer (CRC). We performed a comparative CXCL12/CXCR4 expression analysis and assessed the effect of external CXCL12 stimulation on migration of CRC cells without and with CXCR4 inhibition.

Methods: Expression of CXCL12/CXCR4 was assessed by quantitative real-time PCR, ELISA and immunohistochemistry in resection specimens of 50 CRC patients as well as in the corresponding normal tissues and in three human CRC cell lines with different metastatic potential (Caco-2, SW480 and HT-29).

Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies.

Chemokines have been proposed to contribute to tumour growth and metastatic spread of several cancer entities. Here, we examined the relative levels of CXCL12/CXCR4 in resection specimens from patients with different malignant and non-malignant colorectal diseases as well as colorectal liver metastases (CRLM). CXCL12/CXCR4 mRNA and protein expression profiles were assessed by quantitative real-time PCR, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry in resection specimens from patients with ulcerative colitis (UC; n = 15), colorectal adenoma (CRA; n = 15), colorectal adenocarcinoma (CRC; n = 47) and CRLM (n = 16).

CCL20/CCR6 expression profile in pancreatic cancer.

Background: CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated.

Methods: Using RealTime-PCR, enzyme-linked immunosorbent assay (ELISA), Western Blot and immunohistochemistry, we have analyzed the expression profile of CCL20/CCR6 in resection specimens from patients with chronic pancreatitis (CP) (n = 22), pancreatic cystadenoma (PA) (n = 11) and pancreatic carcinoma (PCA) (n = 25) as well as in the respective matched normal pancreatic tissues.

The chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer.

Chemokines are a superfamily of small chemotactic cytokines, which interact with their G-protein-coupled receptors. These interactions regulate multiple physiological functions, particularly tissue architecture and compartment-specific migration of white blood cells. It has been found that the chemokine/chemokine receptor system has been utilized by cancer cells for migration and metastasis.

Increased growth factor expression after hepatic and pancreatic resection.

Removal of the primary tumour is suggested to associate with an enhanced tumour growth of residual micrometastases. Recent data focus on growth factors that may be released in response to surgery-stimulating receptors of residual tumour cells. Vascular endothelial (VEGF) and hepatocyte growth factor (HGF) are potent inducers of angiogenesis.

Differential CXC receptor expression in colorectal carcinomas.

In this study, we aimed to assess the expression profile of chemokine receptors CXCR1-4 in inflammatory and malignant colorectal diseases and corresponding hepatic metastases of synchronous and metachronous origin to elucidate their role in colorectal cancer (CRC) progression and metastasis. Chemokine receptor expression was assessed by quantitative real-time PCR, immunohistochemistry (IHC) and Western blot analysis in resection specimens from patients with ulcerative colitis (UC, n = 25), colorectal adenomas (CRA, n = 8), different stages of CRC (n = 48) as well as colorectal liver metastases (CRLM) along with their corresponding primary colorectal tumours (n = 16). While none of the chemokine receptors were significantly upregulated or downregulated in UC or CRA tissues, CXC receptors 1, 2 and 4 demonstrated a significant increase in expression in all tumour stages of CRC specimens with CXCR4 correlating with tumour grading (P < 0.

Enhanced ENA-78 and IL-8 expression in patients with malignant pancreatic diseases.

Background/aim: Pancreatic cancer is characterized by perineural invasion, early lymph node and liver metastases, and an extremely dismal prognosis. In the present study we aimed at investigating the expression profile of pro-inflammatory and angiogenic CXC chemokines as potential factors contributing to the aggressive biology of this gastrointestinal malignancy.

Methods: Protein expression profiles of the CXC chemokines growth-related oncogene alpha (GRO-alpha/CXCL1), epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5), granulocyte chemoattractant protein-2 (GCP-2/CXCL6), neutrophil-activating protein-2 (NAP-2/CXCL7), and interleukin-8 (IL-8/CXCL8) were assessed by enzyme-linked immunosorbent assay in pancreatic carcinoma, cancer of the papilla of Vater, pancreatic cystadenoma, and chronic pancreatitis specimens.

ELR+ CXC chemokine expression in benign and malignant colorectal conditions.

Background: CXCR2 chemokine ligands CXCL1, CXCL5 and CXCL6 were shown to be involved in chemoattraction, inflammatory responses, tumor growth and angiogenesis. Here, we comparatively analyzed their expression profile in resection specimens from patients with colorectal adenoma (CRA) (n = 30) as well as colorectal carcinoma (CRC) (n = 48) and corresponding colorectal liver metastases (CRLM) (n = 16).

Methods: Chemokine expression was assessed by microdissection, quantitative real-time PCR (Q-RT-PCR), the enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC).

Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer.

Aim: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM).

Methods: IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16).

Results: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues.