Human periostin gene expression in normal tissues, tumors and melanoma: evidences for periostin production by both stromal and melanoma cells

<p>Abstract</p> <p>Background</p> <p>Recently, periostin (<it>POSTN</it>), a gene encoding a protein with similarity to the fasciclin family and involved in cell survival and angiogenesis, has emerged as a promising marker for tumor progression in various types of human cancers. There is some controversy regarding both <it>POSTN </it>expression levels and the nature of periostin-producing cells within tumors. In this study, we used quantitative RT-PCR to assess periostin gene expression in normal tissues, primary cell cultures, tumor tissues and tumor cell lines.</p> <p>Results</p> <p>Periostin expression levels are highly variable in both normal tissues and tumors and strong <it>POSTN </it>overexpression is mostly detected in tumors from pancreas and liver. <it>POSTN </it>is not expressed in blood cancers. In melanoma samples, average periostin expression is not increased in primary tumors whereas <it>POSTN </it>overexpression was detected in about 60% of melanoma metastatic tumors in the liver or lymph nodes. Identification of the cellular source of periostin production in melanoma metastases -cancer cells or stroma- was assessed by comparing periostin expression in 23 newly-established melanoma cell lines and matched tumors. In contrast to the reduction by more than 99% of <it>COL6A3 </it>stromal marker mRNA in all cell lines, significant <it>POSTN </it>transcription was maintained in some melanoma cell lines, suggesting that both stromal cells and melanoma cells express periostin. The high level of periostin expression in primary cultures of skin fibroblasts suggests that fibroblasts may contribute for a large part to periostin production in melanoma-associated stroma. On the other hand, periostin expression in melanoma cells is probably acquired during the tumorigenic process as 1) normal melanocytes do not express <it>POSTN </it>and 2) melanoma cells from distinct metastases of the same patient were associated with very different levels of periostin expression.</p> <p>Conclusion</p> <p>Our comparative analysis suggests that, although periostin overexpression is clearly detected in some cancers, it is not a general feature of tumors. In melanoma, our study identifies both stromal and melanoma cells as sources of periostin production and correlates <it>POSTN </it>expression levels with increased primary tumor thickness and metastatic process development.</p

Projet Termitofuel: les termites et leurs symbiontes pour mieux valoriser la biomasse ligno-cellulosique

L’exploitation actuelle de la biomasse ligno-cellulosique, extrêmement abondante sur Terre, est liée à la production de déchets relativement peu valorisables. C’est pourquoi le projet TERMITOFUEL étudie la digestion du bois chez les termites, grâce à une approche pluridisciplinaire, en vue d’améliorer la production de bioéthanol de seconde génération. Au sein de l’Unité d’Entomologie Fonctionnelle et Evolutive, l’approche protéomique est employée afin d’identifier les micro-organismes présents dans le tube digestif des termites et caractériser les activités enzymatiques

High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens

After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10−5 of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10−4 to 3 × 10−3, which is 10–10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethé, V. Corbière, I. Théate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249–257)

Creating an enabling environment for investment in climate services: The case of Uruguay’s National Agricultural Information System

Increasingly challenged by climate variability and change, many of the world’s governments have turned to climate services as a means to improve decision making and mitigate climate-related risk. While there have been some efforts to evaluate the economic impact of climate services, little is known about the contexts in which investments in climate services have taken place. An understanding of the factors that enable climate service investment is important for the development of climate services at local, national and international levels. This paper addresses this gap by investigating the context in which Uruguay’s Ministry of Livestock, Agriculture and Fisheries invested in and developed its National System of Agriculture Information (SNIA), a national-level climate service for the agriculture sector. Using qualitative research methods, the paper uses key documents and 43 interviews to identify six factors that have shaped the decision to invest in the SNIA: (1) Uruguay’s focus on sustainable agricultural intensification; (2) previous work on climate change adaptation; (3) the modernization of the meteorological service; (4) the country’s open data policy; (5) the government’s decision to focus the SNIA on near-term (e.g., seasonal) rather than long-term climate risk; and (6) the participation of key individuals. While the context in which these enablers emerged is unique to Uruguay, it is likely that some factors are generalizable to other countries. Social science research needed to confirm the wider applicability of innovation systems, groundwork, data access and champion is discussed

The Atmosphere above Ny-Ålesund – Climate and global warming, ozone and surface UV radiation

The Arctic region is considered to be most sensitive to climate change, with warming in the Arctic occurring considerably faster than the global average due to several positive feedback mechanisms contributing to the “Arctic amplification”. Also the maritime and mountainous climate of Svalbard has undergone changes during the last decades. Here, the focus is set on the current atmospheric boundary conditions for the marine ecosystem in the Kongsfjorden area, discussed in the frame of long-term climatic observations in the larger regional and hemispheric context. During the last century, a general warming is found with temperature increases and precipitation changes varying in strength. During the last decades, a strong seasonality of the warming is observed in the Kongsfjorden area, with the strongest temperature increase occurring during the winter season. The winter warming is related to observed changes in the net longwave radiation. Moreover, changes in the net shortwave are observed during the summer period, attributed to the decrease in reflected radiation caused by the retreating snow cover. Another related aspect of radiation is the intensity of solar ultra-violet radiation that is closely coupled to the abundance of ozone in the column of air overhead. The long term evolution of ozone losses in the Arctic and their connection to climate change are discussed

A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia

Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1–specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus–transformed B cells. The HB-1 gene–encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1–specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1–specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD

Selective cancer-germline gene expression in pediatric brain tumors

Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways