F. nucleatum in esophageal cancer tissues was associated with shorter survival, suggesting a potential role as a prognostic biomarker. F. nucleatum might also contribute to aggressive tumor behavior through activation of chemokines, such as CCL20. Clin Cancer Res; 22(22); 5574-81. ©2016 AACR.

Intestinal trefoil factor (ITF) is an essential regulator of colonic epithelial restitution, the rapid migration of colonocytes over mucosal wounds. High levels of ITF are frequently present in colorectal cancers and derived cell lines. Mucosal restitution requires the detachment of epithelium from substrate, which would be expected to induce apoptosis. However, mice deficient in ITF showed an increase in colonocyte apoptosis unaccompanied by changes in expression of receptor-related (TNFR͞Fas) or stressrelated (Bcl-family) cell death regulators. An ITF-expressing colonic (HT-ITF1) cell line was resistant to apoptosis induced by serum starvation and ceramide. Exogenous ITF also protected another human colonic carcinoma-derived cell line (HCT116) and a nontransformed rat intestinal epithelial cell line (IEC-6) from apoptosis. This effect was abrogated by wortmannin and tyrphostin A25, indicating the potential involvement of phosphatidylinositol 3-kinase and epidermal growth factor (EGF) receptor activation. Expression of phosphorylated Akt, which lies downstream of phosphatidylinositol 3-kinase activation, was elevated in this HT-29-ITF line. p53-dependent cell death in the AGS human gastric cancer cell line after etoposide was similarly inhibited by transient expression of ITF but not a C-terminal truncation mutant of ITF, and it required functional phosphatidylinositol 3-kinase and EGF receptor. These findings support a central role for ITF in the maintenance of intestinal mucosal continuity, and conversely demonstrate the potential for ITF expression to confer resistance of colorectal tumors to therapy.cell survival ͉ signal transduction ͉ cell adhesion ͉ colonic neoplasm ͉ cultured tumor cells R estitution, the ability of epithelial cells to spread and migrate across the basement membrane to cover shallow defects, is the key initial step in repair of mucosal injury and can achieve restoration of mucosal continuity over broad areas of damage within hours (1-3). This resurfacing, which is independent of proliferation, is followed over a period of days by a remodeling phase of epithelial proliferation and differentiation. Brisk restitution after injury is desirable both to limit fluid and electrolyte losses and to prevent diffusion of foreign antigens from the gastrointestinal lumen into local and systemic immune compartments. Both these aspects underlie the morbidity after therapeutic abdominal irradiation, and they limit dose and dose intervals (4).The trefoil peptide family, comprising the intestinal peptide ITF and the gastric peptides SP and pS2, play a critical role in epithelial restitution within the mammalian gastrointestinal tract. These small (7-12-kDa) protease-resistant proteins are abundantly secreted onto the mucosal surface by specialized mucus-secreting cells of the gut. They are rapidly up-regulated at the margins of mucosal injury, and they are believed to promote epithelial cell migration (5, 6). Colonic restitution is absent in mice made ITF deficient by homologous recombination (7), renderi...

The trefoil peptide intestinal trefoil factor (ITF) plays a critical role in the protection of colonic mucosa and is essential to restitution after epithelial damage. These functional properties are accomplished through coordinated promotion of cell migration and inhibition of apoptosis. ITF contains a unique three-looped trefoil motif formed by intrachain disulfide bonds among six conserved cysteine residues, which is thought to contribute to its marked protease resistance. ITF also has a seventh cysteine residue, which permits homodimer formation. A series of cysteine-to-serine substitutions and a C-terminally truncated ITF were made by PCR site-directed mutagenesis. Any alteration of the trefoil motif or truncation resulted in loss of protease resistance. However, neither an intact trefoil domain nor dimerization was required to promote cell migration. This pro-restitution activity correlated with the ability of the ITF mutants to activate mitogen-activated protein (MAP) kinase independent of phosphorylation of the epidermal growth factor (EGF) receptor. In contrast, only intact ITF retained both phosphatidylinositol 3-kinase and the EGF receptor-dependent antiapoptotic effect in HCT116 and IEC-6 cells. The inability to block apoptosis correlated with a loss of trefoil peptide-induced transactivation of the EGF receptor or Akt kinase in HT-29 cells. In addition to defining structural requirements for the functional properties of ITF, these findings demonstrate that distinct intracellular signaling pathways mediate the effects of ITF on cell migration and apoptosis.

Although surgical smoke contains potentially hazardous substances, such as cellular material, blood fragments, microorganisms, toxic gases and vapors, many operating rooms (ORs) do not provide protection from exposure to it. This article reviews the hazards of surgical smoke and the means of protecting OR personnel. Our objectives are to promote surgeons' acceptance to adopt measures to minimize the hazards. Depending on its components, surgical smoke can increase the risk of acute and chronic pulmonary conditions, cause acute headaches; irritation and soreness of the eyes, nose and throat; dermatitis and colic. Transmission of infectious disease may occur if bacterial or viral fragments present in the smoke are inhaled. The presence of carcinogens in surgical smoke and their mutagenic effects are also of concern. This review summarizes previously published reports and data regarding the toxic components of surgical smoke, the possible adverse effects on the health of operating room personnel and measures that can be used to minimize exposure to prevent respiratory problems. To reduce the hazards, surgical smoke should be removed by an evacuation system. Surgeons should assess the potential dangers of surgical smoke and encourage the use of evacuation devices to minimize potential health hazards to both themselves and other OR personnel.

miR-200b regulates ZEB2 expression and thus controls metastasis in gastric cancer.

Serum miRNA-21 is considered to be a novel biomarker for diagnosing ESCC, and it can also be used as a response marker during chemotherapy for ESCC patients.

Mucosal damage induces a massive influx of serum complement components into the lumen. The epithelium produces a number of factors that can potentially ameliorate injury including intestinal trefoil factor (ITF), a small protease-resistant peptide produced and secreted onto the mucosal surface by goblet cells, and decay-accelerating factor (DAF), a protein produced by columnar epithelium which protects the host tissue from autologous complement injury. However, coordination of these intrinsic defensive products has not been delineated. DAF protein and mRNA expression were evaluated by immunoblotting and Northern blotting, respectively. NF-κB-DNA binding activity and DAF promoter activity were assessed by an electrophoretic gel mobility shift assay and a reporter gene luciferase assay, respectively. ITF induced a dose- and time-dependent increase in DAF protein and mRNA expression in human (HT-29 and T84) and rat (IEC-6) intestinal epithelial cells. In differentiated T84 cells grown on cell culture inserts, basolateral stimulation with ITF strongly enhanced DAF expression, but apical stimulation had no effects. The C3 deposition induced by complement activation was significantly blocked by the treatment with ITF. In HT-29 cells, ITF increased the stability of DAF mRNA. ITF also enhanced the promoter activity of the DAF gene via NF-κB motif and induced activation of NF-κB-DNA binding activity. ITF promotes protection of epithelial cells from complement activation via up-regulation of DAF expression, contributing to a robust mucosal defense.

Multiple primary cancers are associated with a history of tobacco and alcohol use, supporting the concept of field cancerization. Synchronous multiple primary cancers may be an independent predictor of poorer long-term survival in patients undergoing resection of esophageal cancers.