Science News, Information and Educational Resources


Science Feed Image

    		•    
    The American Association for Cancer Research (AACR) held an exciting conference on Stem Cells, Development, and Cancer in Vancouver, British Columbia, Canada (March 3–6, 2011). The meeting was cochaired by Geoffrey Wahl, Connie Eaves, and Hans Clevers and was attended by 250 international researchers, 40% of whom were young investigators. Three key themes emerged: (i) heterogeneity in stem cells and cancer, (ii) solid tissue cancer stem cells, and (iii) lessons from development. The interdisciplinary foundation of this meeting was central to its success and appeal, underscoring the value of juxtaposing and interrelating work from the three topics addressed. Cancer Res; 71(17); 5616–20. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On

    The Hedgehog (HH) and TGF-? signaling pathways represent essential regulators of cell proliferation and differentiation during embryogenesis. Pathway deregulation is a characteristic of various cancers. Recently, evidence for a convergence of these pathways at the level of the GLI2 transcription factor in the context of tumor initiation and progression to metastasis has emerged. This short review summarizes recent knowledge about GLI2 function and mechanisms of action downstream of TGF-? in cancer. Cancer Res; 71(17); 5606–10. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On

    Leukocyte infiltrates into or around tumor cell nests are found in the context of protumorigenic inflammation and anticancer immunosurveillance. Hence, the detailed composition, density, architecture, and function of leukocyte infiltrates must be analyzed to understand their prognostic impact. The ectopic presence within tumors of high endothelial venule cells, which are normally characteristic for secondary lymphoid organs, correlates with a more pronounced infiltration by T lymphocytes and has a positive predictive impact on local advanced breast cancer treated with neoadjuvant chemotherapy. Recent progress in the field indicates that immune infiltrates of the primary tumors, as well as of metastases, are not only independent prognostic biomarkers but can also constitute predictive factors, suggesting that the pretherapeutic immune response can determine the efficacy of conventional chemotherapies. Moreover, accumulating evidence indicates that chemotherapy can stimulate anticancer immune responses coupled with an increased intratumoral lymphoid infiltration, which correlates with tumor mass reduction and patient survival. Improved methods for the automation of immunohistochemistry and digitalized image analyses will pave the way to an improved understanding of the complex interplay between cancer parenchyma, stroma, and immune effectors, as well as to the routine evaluation of immune-related parameters to the clinical management of cancer patients. Cancer Res; 71(17); 5601–5. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On

    Toll-like receptor (TLR) agonists are promising adjuvants for immune therapy of cancer, but their potential efficacy as single or combinatorial agents has yet to be fully evaluated. Here, we report that among all TLR agonists tested, dendritic cells (DC) stimulated with the TLR3 agonist polyI:C displayed the strongest activity in stimulating proinflammatory responses and the production of melanoma antigen-specific CD8+ T cells. Simultaneous treatment with TLR7/8 agonists further improved these responses, but the inclusion of bacterial lipopolysaccharide (LPS), a TLR4 agonist, suppressed proinflammatory cytokine production. This inhibition was contingent upon rapid induction of the suppressive cytokine interleukin (IL)-10 by LPS, leading to dysregulated immune responses and it could be reversed by signal transducers and activators of transcription 3 knockdown, p38 blockade or antibodies to IL-10 and its receptor. Our findings show how certain TLR agonist combinations can enhance or limit DC responses associated with antitumor immunity, through their relative ability to induce IL-10 pathways that are immune suppressive. Cancer Res; 71(16); 5467–76. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On

    Recurrent gene fusions involving ETS family genes are a distinguishing feature of human prostate cancers, with TMPRSS2–ERG fusions representing the most common subtype. The TMPRSS2–ERG fusion transcript and its splice variants are well characterized in prostate cancers; however, not much is known about the levels and regulation of wild-type ERG. By employing an integrative approach, we show that the TMPRSS2–ERG gene fusion product binds to the ERG locus and drives the overexpression of wild-type ERG in prostate cancers. Knockdown of TMPRSS2–ERG in VCaP cells resulted in the downregulation of wild-type ERG transcription, whereas stable overexpression of TMPRSS2–ERG in the gene fusion-negative PC3 cells was associated with the upregulation of wild-type ERG transcript. Further, androgen signaling-mediated upregulation of TMPRSS2–ERG resulted in the concomitant upregulation of wild-type ERG transcription in VCaP cells. The loss of wild-type ERG expression was associated with a decrease in the invasive potential of VCaP cells. Importantly, 38% of clinically localized prostate cancers and 27% of metastatic prostate cancers harboring the TMPRSS2–ERG gene fusions exhibited overexpression of wild-type ERG. Taken together, these results provide novel insights into the regulation of ERG in human prostate cancers. Cancer Res; 71(16); 5387–92. ©2011 AACR.
    cancerres.aacrjournals.org   ...Read On


    		   
    You can link to this article on your web site using following code:

    Website Code:

    Forum Code:  




     
    		 
    Comments

    We're looking for comments that are interesting, substantial or highly amusing. If your comments are excessively self-promotional (use your real name, no keywords please), obnoxious, or even worse, boring, you will be banned from commenting. Your comment must be related to the post. Please do not comment on how great or wonderful the post is. All comments are moderated and, if approved, will display in less than 24 hours.


    blog comments powered by Disqus