Clinical application of microRNA in gastric cancer in Eastern Asian area

Recent research has shown that microRNA (miRNA), which is involved in almost every step of gastric carcinogenesis, has broad prospective application in diagnosis and therapy of gastric carcinoma. Eastern Asia (South Korea, Japan and China) has the highest incidence of gastric cancer in the world. There were 988 000 new cases of gastric cancer worldwide and 736 000 deaths in 2008. Approximately 60% of the cases of gastric cancer are found in East Asia (mainly China). We herein provide a brief review of the clinical applications of miRNA, which include the following aspects: (1) miRNA may serve as a potential new generation of tumor markers; (2) a complete miRNA expression profile is highly specific, can reflect the evolutionary lineage and differentiation of tumors, and be used to carry out diversity analysis; (3) detecting specific miRNA expression in peripheral blood will become a new method for diagnosis of gastric cancer; (4) miRNA can predict prognosis of gastric cancer; (5) miRNA has predictive value in determining chemotherapy and radiotherapy resistance; and (6) miRNA could be a type of innovative drug. Finally, we focus on assessing the value of miRNA from laboratory to clinical application and the challenges it faces in East Asia.

Helicobacter pylori:a foodborne pathogen?

Helicobacter pylori(H. pylori) is an organism that is widespread in the human population and is sometimes responsible for some of the most common chronic clinical disorders of the upper gastrointestinal tract in humans, such as chronic-active gastritis, duodenal and gastric ulcer disease, low-grade B-cell mucosa associated lymphoid tissue lymphoma of the stomach, and gastric adenocarcinoma, which is the third leading cause of cancer death worldwide. The routes of infection have not yet been firmly established, and different routes of transmission have been suggested, although the most commonly accepted hypothesis is that infection takes place through the faecal-oral route and that contaminated water and foods might play an important role in transmission of the microorganism to humans. Furthermore, several authors have considered H. pylori to be a foodborne pathogen because of some of its microbiological and epidemiological characteristics. H. pylori has been detected in drinking water, seawater, vegetables and foods of animal origin. H. pylori survives in complex foodstuffs such as milk, vegetables and ready-to-eat foods. This review article presents an overview of the present knowledge on the microbiological aspects in terms of phenotypic characteristics and growth requirements of H. pylori, focusing on the potential role that foodstuffs and water may play in the transmission of the pathogen to humans and the methods successfully used for the detection of this microorganism in foodstuffs and water.

Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

H pylori status and angiogenesis factors in human gastric carcinoma

AIM： To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density （MVD）, thymidine phosphorylase （TP）, vascular endothelial growth factor receptor-1 （VEGF-R1）, p53 and circulating VEGF levels. METHODS： Angiogenic markers were analyzed immunohistochemically in 56 primary gastric cancers. H pylori cytotoxin （vacA） and the cytotoxin-associated gene （cagA） amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELISA, respectively. RESULTS： A total of 69% of patients were positive for circulating IgG antibodies against Hpylori. cagA-positive H pylor/strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was significantly associated with cagA （P = 0.0001）. MVD was significantly correlated with both tumor VEGF expression （r = 0.361, P = 0.009） and serum VEGF levels （r = -0.347, P = 0.041）.Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level （P = 0.026）. CONCLUSION： H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic characteristics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical disease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

Pesticides: An Overview of the Current Health Problems of Their Use

The necessity to produce increasing quantities of food to meet the demand of ever-increasing populations has led to the massive use of pesticides in agriculture. Their massive consumption derives from the need to subtract food from competition of fungi, bacteria, and insects and agricultural land from the invasion of competing weeds. Modern agriculture floats on an ocean of synthetic chemical compounds used to crop protection and food preservation during storage. Presently, worldwide about 2000 active ingredients have been listed, categorized into about 60 classes of chemicals. In the world, the overall pesticides, used in agriculture, are about 4.1 million tonnes/years. The exposure of animals and humans to pesticides could be related to neurotoxicity, endocrine disruption, liver and kidney damage, cancer, reproductive effects (sperm abnormalities, decreased fertility, fetal growth retardation, birth defects, or spontaneous abortion), and growth modifications. However, the knowledge about their potential damage to the organs of reproduction, breastfeeding, and infants is still largely insufficient. It is necessary to improve new methods to identify and regulate the long-term safety of pesticides use, to protect the environment and health, and to eliminate the adverse effect of pesticides on the environment and non-target organisms. The assessment of possible risks of old and new pesticides must be increased to include the possible effects on reproduction on animals and pregnancy loss even after a long time. In the meantime, it is necessary to minimize the use of synthetic chemical compounds by increasing the use of biological systems.

T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

HVEM,a cosignaling molecular switch,and its interactions with BTLA,CD160 and LIGHT

Temporal and spatial expression of cosignaling receptors and their ligands regulates the early stages of T-cell activation(signal 1,T-cell receptor(TCR)signaling and signal 2,costimulation/coinhibition),clonal expansion and T-cell survival during their differentiation towards effector T cells.Once the inflammatory stimulus is eliminated,effector T cells return to homeostasis after undergoing a contraction phase by activation-induced cell death and the intervention of ligands for coinhibitory receptors,leaving a population of long-term memory T cells.The expression of ligands for coinhibitory receptors on hematopoietic cells and,more importantly,on non-hematopoietic cells of peripheral tissues is a key process in tuning the functional activity of effector T cells to prevent excess tissue inflammation that may lead to immunopathology and subsequent tissue dysfunction.

Correction to: T follicular helper expansion and humoralmediated rejection are independent of the HVEM/BTLA pathway

In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”,in the acknowledgments section.The correct acknowledgement is as follows:“This work has been supported by grants of the Spanish Ministry of Health(Fondo de Investigaciones Sanitarias,PI13/00029,Spanish Government and co-funded by European Union ERDF/ESF,“Investing in your future”),Department of Education of Castilla and Leon Regional Government(Grant#LE093U13)and Mutua Madrileña Foundation(Basic research grants 2012)to J.I.R.B.;by Miguel Servet National Program(Ministry of National Health)CP12/03063 and by Gerencia Regional de Salud GRS963/A/2014 to M.L.R.G.We are particularly grateful to Mr.Leonides Alaiz for outstanding animal husbandry.”The authors regret the errors.

Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression

The progression of acute myeloid leukemia(AML)—the most severe blood/bone marrow cancer—is determined by the ability of malignant cells to escape host immune surveillance.However,the systemic regulatory mechanisms underlying this phenomenon remain largely unknown.In this study,we discovered a fundamental systemic biochemical strategy that allows AML cells to employ physiological systems within the body to survive and escape immune attack.We found that AML cells use a crucial human adrenal cortex hormone(cortisol)to induce the expression of neuronal receptor latrophilin 1(LPHN1),which facilitates exocytosis.This receptor interacts with the blood plasma protein fibronectin leucine rich transmembrane protein 3(FLRT3)to cause secretion of the immune suppressor galectin-9,which impairs the anticancer activities of cytotoxic lymphoid cells.