Botulinum toxin A complex exploits intestinal M cells to enter the host and exert neurotoxicity.

To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse the intestinal epithelial barrier. However, the mechanism by which BoNT crosses the intestinal epithelial barrier remains unclear. BoNTs are produced along with one or more non-toxic components, with which they form progenitor toxin complexes (PTCs).

Epigenetic modifications of the immune system in health and disease.

Vertebrate animals have developed sophisticated host defense mechanisms against potentially hostile antigens. These mechanisms mainly involve the immune system and the epithelial cells that cover the body surface. Accumulating studies have revealed that epigenetic mechanisms in collaboration with signal transduction networks regulate gene expression over the course of differentiation, proliferation and function of immune and epithelial cells.

The AURKA/TPX2 axis drives colon tumorigenesis cooperatively with MYC.

Background: The MYC oncogene has long been established as a central driver in many types of human cancers including colorectal cancer. However, the realization of MYC-targeting therapies remains elusive; as a result, synthetic lethal therapeutic approaches are alternatively being explored. A synthetic lethal therapeutic approach aims to kill MYC-driven tumors by targeting a certain co-regulator on the MYC pathway.

Simulation model of a lever-propelled wheelchair.

Wheelchair efficiency depends significantly on the individual adjustment of the wheelchair propulsion interface. Wheelchair prescription involves reconfiguring the wheelchair to optimize it for specific user characteristics. Wheelchair tuning procedure is a complicated task that is performed usually by experienced rehabilitation engineers.

Histologic categorization of desmoplastic reaction: its relevance to the colorectal cancer microenvironment and prognosis.

Background: Although the essential roles of stromata in tumor development have been recognized, the morphologic classification of desmoplastic reaction (DR) in colorectal cancer (CRC) is unclear.

Methods: In this study, DRs were histologically classified into three patterns based on the products of activated fibroblasts (i.e.

The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond.

The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane.

Epithelial-stromal interaction via Notch signaling is essential for the full maturation of gut-associated lymphoid tissues.

Intrinsic Notch signaling in intestinal epithelial cells restricts secretory cell differentiation. In gut-associated lymphoid tissue (GALT), stromal cells located beneath the follicle-associated epithelium (FAE) abundantly express the Notch ligand delta-like 1 (Dll1). Here, we show that mice lacking Rbpj-a gene encoding a transcription factor implicated in Notch signaling-in intestinal epithelial cells have defective GALT maturation.

Visualization of the entire differentiation process of murine M cells: suppression of their maturation in cecal patches.

The microfold (M) cell residing in the follicle-associated epithelium is a specialized epithelial cell that initiates mucosal immune responses by sampling luminal antigens. The differentiation process of M cells remains unclear due to limitations of analytical methods. Here we found that M cells were classified into two functionally different subtypes based on the expression of Glycoprotein 2 (GP2) by newly developed image cytometric analysis.

Commensal microbiota regulates T cell fate decision in the gut.

Commensal microbiota shapes the intestinal immune system by regulating T helper (TH) cell lineage differentiation. For example, Bacteroides fragilis colonization not only optimizes the systemic TH1/TH2 balance, but also can induce regulatory T (Treg) cell differentiation in the gut. In addition, segmented filamentous bacteria (SFB) facilitate the development of TH17 cells in the small intestine.

Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer.

Although there have been multiple advances in the development of novel anticancer agents and operative procedures, prognosis of patients with advanced gastric cancer remains poor, especially in patients with peritoneal metastasis. In this study, we established nanoparticles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminated xenografts of human gastric cancer were established in nude mice.

Prognostic impact of histological categorisation of epithelial-mesenchymal transition in colorectal cancer.

Background: The crosstalk between cancer cells and stroma is involved in the acquired capability for metastasis through the induction of epithelial-mesenchymal transition (EMT). We aimed to clarify the prognostic value of the histological category of EMT in colorectal cancer (CRC).

Methods: Tumour EMT was graded into one of three histological categories on the basis of integrated assessment of poorly differentiated clusters and pro-EMT desmoplasia at the leading edge of the primary tumour (Histology(EMT)).

Prognostic value of the number and size of venous invasions in pT3 colorectal cancer: a prospective observational study.

Background: Although venous invasion is reportedly a clinically useful prognostic marker for colorectal cancer, suitable grading criteria have not been established.

Objective: This prospective observational study aimed to investigate the prognostic value of the number and size of venous invasions in patients with pT3 colorectal cancer.

Methods: We recruited 139 consecutive patients with pT3 colorectal carcinomas resected between October 2001 and August 2003.

Preoperative chemoradiation therapy for esophageal cancer is a risk factor for the elevation of high mobility group box-1, leading to an increase in postoperative severe pulmonary complications.

We herein clarified the time course of changes in the serum high mobility group box chromosomal protein-1 (HMGB-1) concentrations in esophageal cancer patients after esophagectomy, and investigated whether the perioperative serum HMGB-1 levels correlate with the administration of neoadjuvant chemoradiation therapy (NACRT) and the postoperative clinical course, especially the occurrence of pulmonary complications, in such patients. Sixty patients who underwent right transthoracic esophagectomy for esophageal cancer were enrolled in this study. The relationship between the perioperative serum HMGB-1 levels and NACRT, and the postoperative severe pulmonary complications were evaluated.

Impact of the perioperative neutrophil-to-lymphocyte ratio on the long-term survival following an elective resection of colorectal carcinoma.

Purposes: The present study was designed to evaluate the prognostic value of the perioperative neutrophil-to-lymphocyte ratio (NLR) for the long-term survival in patients with colorectal cancer.

Methods: This was a retrospective study of 524 patients with histologically proven stage II or III colorectal cancer who underwent curative colorectal resection. We classified patients into a low NLR group or high NLR group base on their NLR values at three time points (before surgery (Pre), on the first postoperative day (POD1), and on the third or fourth postoperative day (POD3)) and evaluated the survival according to the group.

Gut microbiota-generated metabolites in animal health and disease.

Gut microbiota is found in virtually any metazoan, from invertebrates to vertebrates. It has long been believed that gut microbiota, more specifically, the activity of the microbiome and its metabolic products, directly influence a variety of aspects in metazoan physiology. However, the exact molecular relationship among microbe-derived gut metabolites, host signaling pathways, and host physiology remains to be elucidated.

Histologic categorization of fibrotic cancer stroma in the primary tumor is an independent prognostic index in resectable colorectal liver metastasis.

Although the molecular mechanism of desmoplastic reaction (DR) for providing aggressive tumor characteristics is increasingly recognized, the prognostic role of DR has not been investigated in colorectal liver metastasis (CRLM). A pathologic review of 412 patients who underwent hepatectomy for CRLM at 2 independent institutions was conducted. DR in primary tumors was classified as mature, intermediate, or immature on the basis of the existence of keloid-like collagen and myxoid stroma-distinctive histologic products of extracellular matrix remodeling.

Potential causes of stage migration and their prognostic implications in colon cancer: a nationwide survey of specialist institutions in Japan.

Objective: The actual status of stage migration in colon cancer that occurs in the procedure of preparing pathological specimens of lymph nodes has not been fully investigated.

Methods: A nationwide survey of specialist institutions for colon cancer treatment was conducted to clarify interinstitutional differences in processing surgical specimens. After categorizing 111 institutions on the basis of their practice of processing specimens, distribution of tumor stage and the recurrence status of 3294 colon cancer patients treated with the same level of lymphadenectomy were compared.

The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells.

Intestinal regulatory T cells (Treg cells) are necessary for the suppression of excessive immune responses to commensal bacteria. However, the molecular machinery that controls the homeostasis of intestinal Treg cells has remained largely unknown. Here we report that colonization of germ-free mice with gut microbiota upregulated expression of the DNA-methylation adaptor Uhrf1 in Treg cells.

[Risk factors and prevention of surgical site infection for colorectal surgery].

Surgical site infection (SSI), the most frequent adverse event after colorectal surgery, leads to longer hospital days and increased healthcare costs. The development of SSI depends on a complex interplay between patient-related and procedure-related factors. This review refers to the several risk factors for the development of SSI and the risk factor index which were indicated by National Nosocomial Infections Surveillance.

CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer.

Background: CD8+ cytotoxic T cells and forkhead box P3 (FOXP3)+ regulatory T cells are major players in tumor immunity. Increased CD8+ tumor-infiltrating lymphocytes (TILs) and high CD8/FOXP3 TIL ratios are associated with improved survival. Neoadjuvant chemoradiotherapy (CRT) can result in tumor regression; however, immunomodulation during CRT for rectal cancer has not been thoroughly assessed.

Influence of fish to soybean oil ratio on hepatic mononuclear cell function and survival after intraportal bacterial challenge in parenterally fed mice.

Background: Parenteral nutrition (PN) is indispensable for meeting the caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition. However, PN decreases hepatic mononuclear cell (MNC) numbers and impairs their functions. We examined the effects of various ratios of ω-3 to ω-6 polyunsaturated fatty acids on hepatic MNC number and function in a murine model.

Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters.

Allelic imbalance at an 8q24 oncogenic SNP is involved in activating MYC in human colorectal cancer.

Background: The rs6983267 at 8q24.21 has been established as a significant cancer-related single nucleotide polymorphism (SNP). The risk allele showed similarity to the binding site of transcription factor TCF4/LEF1 that activates transcription of MYC.

Risk factors for surgical site infection in Japanese patients with ulcerative colitis: a multicenter prospective study.

Purpose: A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC).

Methods: From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI.

Selection of an aptamer against mouse GP2 by SELEX.

Microfold (M) cells are intestinal epithelial cells specialized for sampling and transport of luminal antigens to gut-associated lymphoid tissue for initiation of both mucosal and systemic immune responses. Therefore, M-cell targeted vaccination has the potential to be a better immunization strategy. Glycoprotein 2 (GP2), an antigen uptake receptor for FimH(+) bacteria on M cells, can be a good target for this purpose.