Colon cancer cells produce immunoregulatory glucocorticoids

Glucocorticoids (GC) have important anti-inflammatory and pro-apoptotic activities. Initially thought to be exclusively produced by the adrenal glands, there is now increasing evidence for extra-adrenal sources of GCs. We have previously shown that the intestinal epithelium produces immunoregulatory GCs and that intestinal steroidogenesis is regulated by the nuclear receptor liver receptor homolog-1 (LRH-1). As LRH-1 has been implicated in the development of colon cancer, we here investigated whether LRH-1 regulates GC synthesis in colorectal tumors and whether tumor-produced GCs suppress T-cell activation. Colorectal cancer cell lines and primary tumors were found to express steroidogenic enzymes and regulatory factors required for the de novo synthesis of cortisol. Both cell lines and primary tumors constitutively produced readily detectable levels of cortisol, as measured by radioimmunoassay, thin-layer chromatography and bioassay. Whereas overexpression of LRH-1 significantly increased the expression of steroidogenic enzymes and the synthesis of cortisol, downregulation or inhibition of LRH-1 effectively suppressed these processes, indicating an important role of LRH-1 in colorectal tumor GC synthesis. An immunoregulatory role of tumor-derived GCs could be further confirmed by demonstrating a suppression of T-cell activation. This study describes for the first time cortisol synthesis in a non-endocrine tumor in humans, and suggests that the synthesis of bioactive GCs in colon cancer cells may account as a novel mechanism of tumor immune escape.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite

Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination.

Inadequate quality of surveillance after curative surgery for colon cancer

Colon cancer patients are at risk for recurrence. Recurrent disease might be curable if detected early by surveillance. However, data on the quality of surveillance are scarce. The objective of this study is to analyze the quality of surveillance after curative surgery for colon cancer among a cohort of Swiss patients.

[Proteins in rheumatology and clinical immunology]

Twelve years ago the tumour necrosis factor (TNF) inhibitors revolutionised the therapy of rheumatoid arthritis and other inflammatory rheumatic diseases. Today, in addition to anti-cytokine strategies, immunosuppressive biologicals have been developed that delete B-lymphocytes or inhibit the activation of T-lymphocytes. The spectrum of indications for these protein drugs will broaden substantially in the near future and will likely include also diseases with orphan status (incidence below 1:10'000). Used in the right indication and with knowledge of molecular effects as well as clinical adverse effects these new drugs do not appear to be more dangerous than conventional disease modifying agents (DMARDs).

Wild immunology: converging on the real world

Recently, the Centre for Immunity, Infection and Evolution sponsored a one-day symposium entitled "Wild Immunology." The CIIE is a new Wellcome Trust-funded initiative with the remit to connect evolutionary biology and ecology with research in immunology and infectious diseases in order to gain an interdisciplinary perspective on challenges to global health. The central question of the symposium was, "Why should we try to understand infection and immunity in wild systems?" Specifically, how does the immune response operate in the wild and how do multiple coinfections and commensalism affect immune responses and host health in these wild systems? The symposium brought together a broad program of speakers, ranging from laboratory immunologists to infectious disease ecologists, working on wild birds, unmanaged animals, wild and laboratory rodents, and on questions ranging from the dynamics of coinfection to how commensal bacteria affect the development of the immune system. The meeting on wild immunology, organized by Amy Pedersen, Simon Babayan, and Rick Maizels, was held at the University of Edinburgh on 30 June 2011.

Colon cancer cells produce immunoregulatory glucocorticoids

Expression or release of immunosuppressive molecules may protect tumor cells from the recognition and destruction by the immune system. New findings indicate that colorectal tumors produce immunoregulatory glucocorticoids and thereby suppress immune cell activation. The nuclear receptor LRH-1 plays a critical role in the regulation of colorectal tumor proliferation and glucocorticoid synthesis.

High HSP27 and HSP70 expression levels are independent adverse prognostic factors in primary resected colon cancer

The expression of Heat Shock Proteins (HSPs) is increased in various cancers and has been shown to correlate with biological tumor behaviour. This study aimed to investigate the impact of HSP70, HSP60 and HSP27 expression in colon cancer.

Tissue-based proteomics reveals FXYD3, S100A11 and GSTM3 as novel markers for regional lymph node metastasis in colon cancer

Regional lymph node metastasis negatively affects prognosis in colon cancer patients. The molecular processes leading to regional lymph node metastasis are only partially understood and proteomic markers for metastasis are still scarce. Therefore, a tissue-based proteomic approach was undertaken for identifying proteins associated with regional lymph node metastasis. Two complementary tissue-based proteomic methods have been employed. MALDI imaging was used for identifying small proteins (≤25 kDa) in situ and label-free quantitative proteomics was used for identifying larger proteins. A tissue cohort comprising primary colon tumours without metastasis (UICC II, pN0, n = 21) and with lymph node metastasis (UICC III, pN2, n = 33) was analysed. Subsequent validation of identified proteins was done by immunohistochemical staining on an independent tissue cohort consisting of primary colon tumour specimens (n = 168). MALDI imaging yielded ten discriminating m/z species, and label-free quantitative proteomics 28 proteins. Two MALDI imaging-derived candidate proteins (FXYD3 and S100A11) and one from the label-free quantitative proteomics (GSTM3) were validated on the independent tissue cohort. All three markers correlated significantly with regional lymph node metastasis: FXYD3 (p = 0.0110), S100A11 (p = 0.0071), and GSTM3 (p = 0.0173). FXYD3 and S100A11 were more highly expressed in UICC II patient tumour tissues. GSTM3 was more highly expressed in UICC III patient tumour tissues. By our tissue-based proteomic approach, we could identify a large panel of proteins which are associated with regional lymph node metastasis and which have not been described so far. Here we show that novel markers for regional lymph metastasis can be identified by MALDI imaging or label-free quantitative proteomics and subsequently validated on an independent tissue cohort. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Update in clinical allergy and immunology

In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field.

Myoelectric activity of the ileum, cecum, proximal loop of the ascending colon, and spiral colon in cows with naturally occurring cecal dilatation-dislocation

OBJECTIVE: To analyze myoelectric activity of the ileum, cecum, proximal loop of the ascending colon (PLAC), and spiral colon in cows with naturally occurring cecal dilatation-dislocation (CDD) and compare findings with those in healthy cows. ANIMALS: 8 CDD-affected and 6 healthy control cows. PROCEDURES: Immediately after diagnosis, CDD-affected cows underwent surgery; control cows underwent a similar surgical procedure. Before completion of surgery, 8 bipolar silver electrodes were implanted in the ileum (n = 2), cecum (1), PLAC (1), and spiral colon (4) of each cow. Beginning the day after surgery, intestinal myoelectric activity was recorded daily (8-hour period) for 4 days; data were analyzed by use of specialized software programs. Quantitative variables of myoelectric activity were compared between groups. RESULTS: Cows of both groups recovered without complications after surgery. In control cows, physiologic myoelectric activity was recorded in all intestinal segments on all days after surgery. Apparently normal myoelectric activity was evident in the ileum of CDD-affected cows on the first day after surgery, but myoelectric activity patterns in the cecum, PLAC, and spiral colon were variable with no organized cyclic myoelectric patterns, incomplete or normally organized migrating myoelectric complexes, and slow normalization over time. CONCLUSIONS AND CLINICAL RELEVANCE: After surgery for CDD, normal myoelectric patterns were disrupted in the large intestine of cows, especially in the spiral colon. Clinical recovery with effective transit of ingesta occurred before normalization of myoelectric activity in the large intestine. Therapeutic protocols for restoration or normalization of spiral colon motility should be developed for treatment of CDD-affected cattle.

A global ”imaging” view on systems approaches in immunology

The immune system exhibits an enormous complexity. High throughput methods such as the "-omic'' technologies generate vast amounts of data that facilitate dissection of immunological processes at ever finer resolution. Using high-resolution data-driven systems analysis, causal relationships between complex molecular processes and particular immunological phenotypes can be constructed. However, processes in tissues, organs, and the organism itself (so-called higher level processes) also control and regulate the molecular (lower level) processes. Reverse systems engineering approaches, which focus on the examination of the structure, dynamics and control of the immune system, can help to understand the construction principles of the immune system. Such integrative mechanistic models can properly describe, explain, and predict the behavior of the immune system in health and disease by combining both higher and lower level processes. Moving from molecular and cellular levels to a multiscale systems understanding requires the development of methodologies that integrate data from different biological levels into multiscale mechanistic models. In particular, 3D imaging techniques and 4D modeling of the spatiotemporal dynamics of immune processes within lymphoid tissues are central for such integrative approaches. Both dynamic and global organ imaging technologies will be instrumental in facilitating comprehensive multiscale systems immunology analyses as discussed in this review.

Maintenance of skills, competencies, and performance in allergy and clinical immunology: time to lay the foundation for a universal approach

Allergist/clinical immunologist maintenance of certification and training program reaccreditation are mandatory in some countries. The World Allergy Organization conducted surveys in 2009 and 2011 to assess where such programs were available and to promote the establishment of such programs on a global level. This was done with the presumption that after such an "inventory," World Allergy Organization could offer guidance to its Member Societies on the promotion of such programs to assure the highest standards of practice in the field of allergy and clinical immunology. This review draws on the experience of countries where successful programs are in place and makes recommendations for those wishing to implement such programs for the specialty.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases.