Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma. A clinicobiological study of the GELA.

Background In angioimmunoblastic T-cell lymphoma, symptoms linked to B-lymphocyte activation are common, and variable numbers of CD20(+) large B-blasts, often infected by Epstein-Barr virus, are found in tumor tissues. We postulated that the disruption of putative B-T interactions and/or depletion of the Epstein-Barr virus reservoir by an anti-CD20 monoclonal antibody (rituximab) could improve the clinical outcome produced by conventional chemotherapy. DESIGN AND METHODS: Twenty-five newly diagnosed patients were treated, in a phase II study, with eight cycles of rituximab + chemotherapy (R-CHOP21). Tumor infiltration, B-blasts and Epstein-Barr virus status in tumor tissue and peripheral blood were fully characterized at diagnosis and were correlated with clinical outcome. RESULTS: A complete response rate of 44% (95% CI, 24% to 65%) was observed. With a median follow-up of 24 months, the 2-year progression-free survival rate was 42% (95% CI, 22% to 61%) and overall survival rate was 62% (95% CI, 40% to 78%). The presence of Epstein-Barr virus DNA in peripheral blood mononuclear cells (14/21 patients) correlated with Epstein-Barr virus score in lymph nodes (P<0.004) and the detection of circulating tumor cells (P=0.0019). Despite peripheral Epstein-Barr virus clearance after treatment, the viral load at diagnosis (>100 copy/μg DNA) was associated with shorter progression-free survival (P=0.06). Conclusions We report here the results of the first clinical trial targeting both the neoplastic T cells and the microenvironment-associated CD20(+) B lymphocytes in angioimmunoblastic T-cell lymphoma, showing no clear benefit of adding rituximab to conventional chemotherapy. A strong relationship, not previously described, between circulating Epstein-Barr virus and circulating tumor cells is highlighted

Genetic modification for disease resistance: a position paper

This Position Paper was prepared by members of the Task Force on Global Food Security of the International Society for Plant Pathology. An objective approach is proposed to the assessment of the potential of genetic modification (GM) to reduce the impact of crop diseases. The addition of GM to the plant breeder’s conventional toolbox facilitates gene-by-gene introduction into breeding programmes of well defined characters, while also allowing access to genes from a greatly extended range of organisms. The current status of GM crops is outlined. GM could make an additional contribution to food security but its potential has been controversial, sometimes because of fixed views that GM is unnatural and risky. These have no factual basis: GM technology, where adopted, is widely regulated and no evidence has been reported of adverse consequences for human health. The potential benefits of GM could be particularly valuable for the developing world but there are numerous constraints. These include cost, inadequate seed supply systems, reluctance to adopt unfamiliar technology, concern about markets, inadequacy of local regulatory systems, mismatch between research and growers’ needs, and limited technical resources. The lower cost of new gene-editing methods should open the practice of GM beyond multinational corporations. As yet there are few examples of utilization of GM-based resistance to plant diseases. Two cases, papaya ringspot virus and banana xanthomonas wilt, are outlined. In the developing world there are many more potential cases whose progress is prevented by the absence of adequate biosafety regulation. It is concluded that there is untapped potential for using GM to introduce disease resistance. An objective approach to mobilizing this potential is recommended, to address the severe impact of plant disease on food security

Development of a kinetic metabolic model: application to Catharanthus roseus hairy root

A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was described as a function of intracellular concentration in cell building blocks. Intracellular transport and accumulation kinetics for major nutrients were included. The model uses intracellular nutrients as well as energy shuttles to describe metabolic regulation. Model calibration was performed using experimental data obtained from batch and medium exchange liquid cultures of C. roseus hairy root using a minimal medium in Petri dish. The model is efficient in estimating the growth rate

Biotechnologizing Jatropha for local sustainable developments

This article explores whether and how the biotechnologization process that the fuel-plant Jatropha curcas is undergoing might strengthen local sustainable development. It focuses on the ongoing efforts of the multi-stakeholder network Gota Verde to harness Jatropha within local small-scale production systems in Yoro, Honduras. It also looks at the genomics research on Jatropha conducted by the Dutch research institute Plant Research International, specifically addressing the ways in which that research can assists local development in Honduras. A territorial approach is applied for analysis employing a three domain concept (local sustainable biotechnological development) of territory, technology and re-territorialization. The article suggests that, although the biotechnologization process (through genomics) of Jatropha within the socio-technical framework of the institute and multi-stakeholder networks is an ongoing process¿¿and different trajectories are, therefore, still open - the process can, nevertheless, strengthen local sustainable developmen

MicroRNA expression profiles during cotton (Gossypium hirsutum L) fiber early development

The role of microRNAs (miRNAs) during cotton fiber development remains unclear. Here, a total of 54 miRNAs belonging to 39 families were selected to characterize miRNA regulatory mechanism in eight different fiber development stages in upland cotton cv BM-1. Among 54 miRNAs, 18 miRNAs were involved in cotton fiber initiation and eight miRNAs were related to fiber elongation and secondary wall biosynthesis. Additionally, 3,576 protein-coding genes were candidate target genes of these miRNAs, which are potentially involved in cotton fiber development. We also investigated the regulatory network of miRNAs and corresponding targets in fiber initiation and elongation, and secondary wall formation. Our Gene Ontology-based term classification and KEGG-based pathway enrichment analyses showed that the miRNA targets covered 220 biological processes, 67 molecular functions, 45 cellular components, and 10 KEGG pathways. Three of ten KEGG pathways were involved in lignan synthesis, cell elongation, and fatty acid biosynthesis, all of which have important roles in fiber development. Overall, our study shows the potential regulatory roles of miRNAs in cotton fiber development and the importance of miRNAs in regulating different cell types. This is helpful to design miRNA-based biotechnology for improving fiber quality and yield

Arabidopsis Plasmodesmal Proteome

The multicellular nature of plants requires that cells should communicate in order to coordinate essential functions. This is achieved in part by molecular flux through pores in the cell wall, called plasmodesmata. We describe the proteomic analysis of plasmodesmata purified from the walls of Arabidopsis suspension cells. Isolated plasmodesmata were seen as membrane-rich structures largely devoid of immunoreactive markers for the plasma membrane, endoplasmic reticulum and cytoplasmic components. Using nano-liquid chromatography and an Orbitrap ion-trap tandem mass spectrometer, 1341 proteins were identified. We refer to this list as the plasmodesmata- or PD-proteome. Relative to other cell wall proteomes, the PD-proteome is depleted in wall proteins and enriched for membrane proteins, but still has a significant number (35%) of putative cytoplasmic contaminants, probably reflecting the sensitivity of the proteomic detection system. To validate the PD-proteome we searched for known plasmodesmal proteins and used molecular and cell biological techniques to identify novel putative plasmodesmal proteins from a small subset of candidates. The PD-proteome contained known plasmodesmal proteins and some inferred plasmodesmal proteins, based upon sequence or functional homology with examples identified in different plant systems. Many of these had a membrane association reflecting the membranous nature of isolated structures. Exploiting this connection we analysed a sample of the abundant receptor-like class of membrane proteins and a small random selection of other membrane proteins for their ability to target plasmodesmata as fluorescently-tagged fusion proteins. From 15 candidates we identified three receptor-like kinases, a tetraspanin and a protein of unknown function as novel potential plasmodesmal proteins. Together with published work, these data suggest that the membranous elements in plasmodesmata may be rich in receptor-like functions, and they validate the content of the PD-proteome as a valuable resource for the further uncovering of the structure and function of plasmodesmata as key components in cell-to-cell communication in plants