F4/80Ly6C Macrophages Lead to Cell Plasticity and Cancer Initiation in Colitis.

Background & Aims: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.

Methods: To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis.

Intestinal Stem Cell Marker ASCL2 is a Novel Prognostic Predictor in Esophageal Adenocarcinoma.

Purpose Intestinal stem cell markers play a significant role in esophageal adenocarcinoma carcinogenesis via Barrett's esophagus; however, its utility as a prognostic biomarker has not been established. Methods We analyzed the immunohistochemical expression of intestinal stem cell markers, ASCL2 and LGR5, using whole slides (35 cases) and tissue microarray (TMA; 64 cases). On TMA slides, adjacent normal squamous epithelium, metaplastic glandular epithelium (Barrett's esophagus), and dysplastic glandular epithelium were inserted when applicable.

scSNV: accurate dscRNA-seq SNV co-expression analysis using duplicate tag collapsing.

Identifying single nucleotide variants has become common practice for droplet-based single-cell RNA-seq experiments; however, presently, a pipeline does not exist to maximize variant calling accuracy. Furthermore, molecular duplicates generated in these experiments have not been utilized to optimally detect variant co-expression. Herein, we introduce scSNV designed from the ground up to "collapse" molecular duplicates and accurately identify variants and their co-expression.

Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor.

Esophageal adenocarcinoma has few known recurrent mutations and therefore robust, reliable and reproducible patient-specific models are needed for personalized treatment. Patient-derived organoid culture is a strategy that may allow for the personalized study of esophageal adenocarcinoma and the development of personalized induction therapy. We therefore developed a protocol to establish EAC organoids from endoscopic biopsies of naïve esophageal adenocarcinomas.

Author Correction: Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

miR-145 expression enhances integrin expression in SK-GT-4 cell line by down-regulating c-Myc expression.

Adenocarcinoma of the esophagus is increasing in frequency and is the 6th most common cause of cancer death in North America. In adenocarcinoma cell lines, we have previously demonstrated that expression of miR-145, leads to enhanced invasion, resistance to anoikis and better attachment to fibronectin in esophageal adenocarcinoma. In contrast, expression of miR-145 acts as a tumor suppressor in squamous cell carcinoma.

Partial Restoration of CFTR Function in cftr-Null Mice following Targeted Cell Replacement Therapy.

Cystic fibrosis (CF) is a fatal recessive genetic disorder caused by a mutation in the gene encoding CF transmembrane conductance regulator (CFTR) protein. Alteration in CFTR leads to thick airway mucus and bacterial infection. Cell therapy has been proposed for CFTR restoration, but efficacy has been limited by low engraftment levels.

Stimulus-dependent dissociation between XB130 and Tks5 scaffold proteins promotes airway epithelial cell migration.

Repair of airway epithelium after injury requires migration of neighboring epithelial cells to injured areas. However, the molecular mechanisms regulating airway epithelial cell migration is not well defined. We have previously shown that XB130, a scaffold protein, is required for airway epithelial repair and regeneration in vivo, and interaction between XB130 and another scaffold protein, Tks5, regulates cell proliferation and survival in human bronchial epithelial cells.

Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6.

MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

Background: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival.

Cancer-associated fibroblasts predict poor outcome and promote periostin-dependent invasion in oesophageal adenocarcinoma.

Interactions between cancer cells and cancer-associated fibroblasts (CAFs) play an important role in tumour development and progression. In this study we investigated the functional role of CAFs in oesophageal adenocarcinoma (EAC). We used immunochemistry to analyse a cohort of 183 EAC patients for CAF markers related to disease mortality.

A comparison of primary oesophageal squamous epithelial cells with HET-1A in organotypic culture.

Background Information: Carcinoma of the oesophagus is the sixth leading cause of cancer death in the western world and is associated with a 5-year survival of less than 15%. Recent evidence suggests that stromal-epithelial interactions are fundamental in carcinogenesis. The advent of co-culture techniques permits the investigation of cross-talk between the stroma and epithelium in a physiological setting.

Hypoxia-induced downregulation of autophagy mediator Beclin 1 reduces the susceptibility of malignant intestinal epithelial cells to hypoxia-dependent apoptosis.

Disruption of tumor blood supply causes tumor hypoxia. Hypoxia can induce cell death, but cancer cells that remain viable in the absence of oxygen often possess an increased survival potential, and tumors formed by these cells tend to grow particularly aggressively. Thus, developing approaches aimed at increasing the susceptibility of malignant cells to hypoxia-induced death represents a potentially important avenue for cancer treatment.

Palmitoylation of the TRAIL receptor DR4 confers an efficient TRAIL-induced cell death signalling.

S-palmitoylation is a lipid modification that regulates membrane-protein association and influences protein trafficking, stability or aggregation, thus playing an important role in protein signalling. We previously demonstrated that the palmitoylation of Fas, one of the DD (death domain)-containing members of the TNFR [TNF (tumour necrosis factor) receptor] superfamily, is essential for the redistribution of this receptor into lipid rafts, an obligatory step for the death signal transmission. Here we investigate the requirement of protein palmitoylation in the activities of other DD-containing death receptors.

Acquisition of anoikis resistance promotes the emergence of oncogenic K-ras mutations in colorectal cancer cells and stimulates their tumorigenicity in vivo.

Detachment from the extracellular matrix causes apoptosis of normal epithelial cells--a phenomenon called anoikis. K-ras oncogene, an established anoikis inhibitor, often occurs in colorectal carcinoma (CRC). In addition to blocking anoikis-inducing mechanisms, oncogenic K-ras can cause anoikis-unrelated changes in CRC cells, such as induction of events promoting their deregulated mitogenesis, ability to trigger angiogenesis, and so on.

Oncogenic Ras inhibits anoikis of intestinal epithelial cells by preventing the release of a mitochondrial pro-apoptotic protein Omi/HtrA2 into the cytoplasm.

Resistance of cancer cells to anoikis, apoptosis induced by cell detachment from the extracellular matrix, is thought to represent a critical feature of the malignant phenotype. Mechanisms that control anoikis of normal and cancer cells are understood only in part. Previously we found that anoikis of non-malignant intestinal epithelial cells is driven by detachment-induced down-regulation of Bcl-X(L), a protein that blocks apoptosis through preventing the release of death-promoting factors from the mitochondria.

Sodium salicylate promotes neutrophil apoptosis by stimulating caspase-dependent turnover of Mcl-1.

Mcl-1 is an antiapoptotic member of the Bcl-2 family of proteins that plays a central role in cell survival of neutrophils and other cells. The protein is unusual among family members in that it has a very short half-life of 2-3 h. In this report, we show that sodium salicylate (at 10 mM) greatly enhances the rate at which neutrophils undergo apoptosis and, in parallel, greatly accelerates the turnover rate of Mcl-1, decreasing its half-life to only 90 min.

ras Oncogene triggers up-regulation of cIAP2 and XIAP in intestinal epithelial cells: epidermal growth factor receptor-dependent and -independent mechanisms of ras-induced transformation.

Detachment of normal epithelial cells from the extracellular matrix (ECM) triggers apoptosis, a phenomenon called anoikis. Conversely, carcinomas (cancers of epithelial origin) represent three-dimensional disorganized multicellular masses in which cells are deprived of adhesion to the ECM but remain viable. Resistance of cancer cells to anoikis is thought to be critical for tumor progression.

Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibition delay neutrophil apoptosis by increasing the stability of Mcl-1.

Human neutrophils normally have a very short half-life and die by apoptosis. Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) can delay this apoptosis via increases in the cellular levels of Mcl-1, an anti-apoptotic protein of the Bcl-2 family with a rapid turnover rate. Here we have shown that inhibition of the proteasome (a) decreases the rate of Mcl-1 turnover within neutrophils and (b) significantly delays apoptosis.