Dendritic cell (DC)-based antitumor vaccine is a novel cancer immunotherapy that is promising for reducing cancer-related mortality. However, results from early clinical trials were suboptimal. A possible explanation is that many tumors secrete immunosuppressive factors such as TGF-β, which may hamper host immune response to DC vaccine. In this study, we demonstrated that TGF-β produced by tumors significantly reduced the potency of DC/tumor fusion vaccines. TGF-β-secreting (CT26-TGF-β) stable mouse colon cancer cell lines were generated using a retroviral vector expressing TGF-β. A non-TGF-β-secreting (CT26-neo) cell line was generated using an empty retroviral vector. The efficacies of DC/tumor fusion vaccines were assessed in vitro and in vivo. DC/CT26-TGF-β fusion cells failed to induce a strong T cell proliferative response in vitro, mainly due to the effect of TGF-β on T cell responsiveness rather than DC stimulatory capability. Animals vaccinated with DC/CT26-TGF-β fusion vaccine had lower tumor-specific CTL activity and had significantly lower survival after tumor challenge as compared with animals immunized with DC/CT26-neo hybrids (45 vs 77%, p < 0.05). Ex vivo exposure of DCs to TGF-β did not appear to lessen the efficacy of DC vaccine. These data suggest that tumor-derived TGF-β reduces the efficacy of DC/tumor fusion vaccine via an in vivo mechanism. Neutralization of TGF-β produced by the fusion cells may enhance the effectiveness of DC-based immunotherapy.

The human ATOH7 gene encodes a basic helix-loop-helix (bHLH) transcription factor that is highly similar to Drosophila Atonal within the conserved bHLH domain. The ATOH7 coding region is contained within a single exon. We mapped ATOH7 to Chromosome (Chr) 10q21.3-22.1, a region syntenic to the segment of mouse Chr 10 where Atoh7 (formerly Math5) is located. The evolutionary relationship between ATOH7 and other atonal homologs was investigated using parsimony analysis. A direct comparison of ATH5/7 and ATH1 protein subgroups to Atonal also revealed a nonrandom distribution of amino acid changes across the bHLH domain, which may be related to their separate visual and proprioceptive sensory functions. Among bHLH genes, ATOH7 is most closely related to Atoh7. This sequence conservation extends significantly beyond the coding region. We define blocks of strong homology in flanking human and mouse genomic DNA, which are likely to include cis regulatory elements. Because targeted deletion of Atoh7 causes optic nerve agenesis in mice, we propose ATOH7 as a candidate for human optic nerve aplasia and related clinical syndromes.Early development of the mammalian retina proceeds through a series of cell fate decisions in which progenitor cells in the optic cup progressively exit mitosis, migrate to specific laminar positions, and terminally differentiate into one of seven basic neural or glial cell types. Defects in retinal cell determination or differentiation lead to specific malformations in humans, including Leber's congenital amaurosis (Freund et al. 1998;Sohocki et al. 1998), cone-rod dystrophy (Freund et al. 1997;Sohocki et al. 1998;Swain et al. 1997), enhanced S-cone syndrome (Cepko 2000;Haider et al. 2000), and optic nerve aplasia or hypoplasia (Lee et al. 1996;Scott et al. 1997;Weiter et al. 1977). Although the genetic basis for retinal histogenesis is poorly understood, recent findings suggest that key proteins controlling some of these developmental processes are nuclear transcription factors Freund et al. 1997;Kobayashi et al. 1999;Swain et al. 1997;Wang et al. 2001).Basic helix-loop-helix (bHLH) transcription factors regulate multiple aspects of retinal neuron formation in vertebrates and invertebrates Vetter and Brown 2001;Cepko 1999). Proneural bHLH proteins contain basic DNA-binding and helix-loop-helix dimerization Correspondence to: T. Glaser; E-mail: tglaser@umich.edu. The nucleotide sequence data reported in this paper have been submitted to GenBank and assigned the accession numbers AF418922 and AF418923. (Jarman et al. 1993). While several vertebrate atonal homologs (Atoh proteins) have been identified, most act only during peripheral or central nervous system development and are not expressed significantly during eye formation. In contrast, the ATH5/7 subclass (named for Xenopus Xath5 and mouse Atoh7) is highly expressed by retinal progenitors during the early stages of eye development in zebrafish, chick, frog, and mouse (Brown et al. 1998;Kanekar et al. 1997;Liu et al. 2001;Masai et al. 2...

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Hg2+captured by wet flue gas desulfurization (WFGD) systems can easily be reduced by reducing substances such as S(IV) (SO32-or HSO3-) and results in emissions of elemental mercury (Hg0). The re-emission of Hg0would lead to a damping of the total mercury removal efficiency by WFGD systems. The effects of the operating conditions, which included the pH, temperature, Cl-concentrations and oxygen concentrations, on Hg0re-emission from WFGD liquors was carried out. The experimental results indicated that the Hg0re-emission rate from WFGD liquors increased as the operational temperatures and pH values increased. The Hg0re-emission rates decreased as the O2concentration of flue gas and Cl-concentration of WFGD liquors increased. So the Hg0re-emission from WFGD system can be reduced or slowed by decreasing the temperature and pH, or by using forced oxidation. The present findings could be valuable for industrial application of characterizing and optimizing mercury control in WFGD systems.