Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.co

Nitric Oxide (NO) and Cyclooxygenase-2 (COX-2) Cross-Talk in Co-Cultures of Tumor Spheroids with Normal Cells

Cyclooxygenases (COX), prostaglandin E2 (PGE2) and nitric oxide (NO) are believed to be some of the most important factors related to colon cancer growth and metastasis. In this study, we aimed to investigate the associations between COX-2, PGE2 and NO in co-cultures of human colon cancer spheroids obtained from different tumor grades with normal human colonic epithelium and myofibroblast monolayers. L-arginine (2 mM), a substrate for nitric oxide synthases (NOS), decreased COX-2 and PGE2 levels, while NG-nitro-L-arginine methyl ester (L-NAME) (2 mM), a NOS inhibitor, had no influence on COX-2 and PGE2 levels but limited tumor cell motility. NS398 (75 μM), a selective COX-2 inhibitor, had no significant influence on NO level but decreased motility of tumor cells. COX-2, PGE2 and NO levels depended on the tumor grade of the cells, being the highest in Duke’s stage III colon carcinoma. Summing up, we showed that addition of L-arginine at doses which did not stimulate NO level caused a significant decrease in COX-2 and PGE2 amounts in co-cultures of colon tumor spheroids with normal epithelial cells and myofibroblasts. Any imbalances in NO level caused by exogenous factors influence COX-2 and PGE2 amounts depending on the kind of cells, their reciprocal interactions and the local microenvironmental conditions. The knowledge of these effects may be useful in limiting colon carcinoma progression and invasion

Revisiting the 'Cotton Problem': A Comparative Analysis of Cotton Reforms in Sub-Saharan Africa

The cotton sector has been amongst the most regulated in Africa, and still is to a large extent in West and Central Africa (WCA), despite repeated refirm recommendations by international donors. On the other hand, orthodox refirms in East and Southern Africa (ESA) have not always yielded the expected results. This paper uses a stylised contracting model to investigate the link between market structure and equity and efficiency in sub-Saharan cotton sectors; explain the outcomes of refirms in ESA; and analyze the potential consequences of orthodox refirms in WCA. We argue that the level of the world price and of government intervention, the nature of pre-refirm institutional organisation, as well as the degree of parastatal inefficiency, all contribute to making refirms less attractive to firmers and governments in WCA today, as compared to ESA in the 1990s.We illustrate our arguments with empirical observations on the perfirmance of cotton sectors across sub-Saharan Africa

Food Standards and Welfare: A General Equilibrium Model with Market Imperfections

We analyze the effects of high standards food chains on household welfare taking into account general equilibrium effects and market imperfections. To measure structural production changes and welfare effects on rural and urban households, our model has two types of agents, five kinds of products and four types of factors. We calibrate the model using dataset from China. The simulation results show that how poor rural households are affected depends on a variety of factors, including the nature of the shocks leading to the expansion of high standards sector, production technologies, trade effects, spillover effects on low standards markets, market imperfections, and labor market effects

Do children do what they say? Responses to hypothetical and real-life social problems in children with mild intellectual disabilities and behaviour problems.

Background Most research on children's social problem-solving skills is based on responses to hypothetical vignettes. Just how these responses relate to actual behaviour in real-life social situations is, however, unclear, particularly for children with mild intellectual disabilities (MID). Method In the present study, the spontaneous and selected responses of 56 children with MID to hypothetical situations from the Social Problem-Solving Test for children with MID (SPT-MID) were compared to their actual behaviour in comparable staged standardized real-life conflict situations. Correlations to externalizing behaviour problems were assessed using the Teacher's Report Form (TRF). Results The results show children with MID and accompanying externalizing behaviour problems to behave more aggressively in the staged real-life conflicts and provide more spontaneous aggressive responses to the hypothetical vignettes than children with MID and no accompanying externalizing behaviour problems; they did not, however, select more aggressive responses from the hypothetical options provided. A moderate correlation was found between the aggressiveness of the spontaneous responses in the hypothetical situations and actual behaviour in the staged real-life situations. In addition, both the spontaneous aggressive responses under hypothetical circumstances and the actual aggressive behaviour under staged real-life circumstances were related to teacher-rated aggressive behaviour in the classroom. Conclusions It is concluded that the hypothetical vignettes from the SPT-MID do provide information on both the actual behaviour and knowledge of social problem-solving skills of children with MID