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Introduction Allograft rejection is unique among immune responses in that it enlists 1%-10% of the total T cell repertoire, a proportion that is 100- to 1000-fold greater than that observed [...], Activation of host T cells that mediate allograft rejection is a 2-step process. The first occurs in secondary lymphoid organs where T cells encounter alloantigens presented by host DCs and differentiate to effectors. Antigen presentation at these sites occurs principally via transfer of intact, donor MHC-peptide complexes from graft cells to host DCs (cross-dressing) or by uptake and processing of donor antigens into allopeptides bound to self-MHC molecules (indirect presentation). The second step takes place in the graft, where effector T cells reengage with host DCs before causing rejection. How host DCs present alloantigens to T cells in the graft is not known. Using mouse islet and kidney transplantation models, imaging cytometry, and 2-photon intravital microscopy, we demonstrate extensive cross-dressing of intragraft host DCs with donor MHC- peptide complexes that occurred early after transplantation, whereas host DCs presenting donor antigen via the indirect pathway were rare. Cross-dressed DCs stably engaged TCR-transgenic effector [CD8.sup.+] T cells that recognized donor antigen and were sufficient for sustaining acute rejection. In the chronic kidney rejection model, cross-dressing declined over time but was still conspicuous 8 weeks after transplantation. We conclude that cross-dressing of host DCs with donor MHC molecules is a major antigen presentation pathway driving effector T cell responses within allografts.

Summary: Recent advances have facilitated studies of the clonal architecture of the aging haematopoietic system, and provided clues to the mechanisms underlying the origins of hematopoietic malignancy. Much less is known about the clonal composition of haematopoiesis and its impact in bone marrow failure (BMF) disorders, including Fanconi anaemia (FA). Understanding clonality in FA is likely to inform both the marked predisposition to cancer and the rapid erosion of regenerative reserve seen with this disease. This may also hold broader lessons for haematopoietic stem cell biology in other diseases with a clonal restriction. In this review, we focus on the conceptual basis and available tools to study clonality, and highlight insights in somatic mosaicism and malignant evolution in FA in the context of haematopoietic failure and gene therapy. [ABSTRACT FROM AUTHOR]

A large, highly symmetric bis-urea macrocycle are easily synthesized from commercially available materials. The formation of the noncovalent porous solids creates a robust activity that could reversibly bind and exchange guest acetic acid molecules.

A constitutional isomeric library synthesized by a modular approach has been used to discover six amphiphilic Janus dendrimer primary structures, which self-assemble into uniform onion-like vesicles with predictable dimensions and number of internal bilayers. These vesicles, denoted onion-like dendrimersomes, are assembled by simple injection of a solution of Janus dendrimer in a water-miscible solvent into water or buffer. These dendrimersomes provide mimics of double-bilayer and multibilayer biological membranes with dimensions and number of bilayers predicted by the Janus compound concentration in water. The simple injection method of preparation is accessible without any special equipment, generating uniform vesicles, and thus provides a promising tool for fundamental studies as well as technological applications in nanomedicine and other fields. [ABSTRACT FROM AUTHOR]

Hematogeneous metastasis can occur via a cascade of circulating tumor cell adhesion events to the endothelial lining of the vasculature, i.e. the metastatic cascade. Interestingly, the pro-inflammatory cytokines IL-6 and TNF- α, which play an important role in potentiating the inflammatory cascade, are significantly elevated in metastatic breast cancer (BCa) patients. Despite their high metastatic potential, human breast carcinoma cells MDA-MB-231 lack interactions with E- selectin functionalized surfaces under physiological shear stresses. We hypothesized that human plasma, 3-D tumor spheroid culture, and cytokine-supplemented culture media could induce a phenotypic switch that allows BCa cells to interact with E-selectin coated surfaces under physiological flow. Flow cytometry, immunofluorescence imaging, and flow- based cell adhesion assay were utilized to investigate the phenotypic changes of MDA-MB-231 cells with various treatments. Our results indicate that plasma, IL-6, and TNF- α promote breast cancer cell growth as aggregates and induce adhesive recruitment of BCa cells on E-selectin coated surfaces under flow. 3-D tumor spheroid culture exhibits the most significant increases in the interactions between BCa and E-selectin coated surfaces by upregulating CD44V4 and sLex expression. Furthermore, we show that IL-6 and TNF- α concentrations in blood may regulate the recruitment of BCa cells to the inflamed endothelium. Finally, we propose a mechanism that could explain the invasiveness of 'triple-negative' breast cancer cell line MDA-MB-231 via a positive feedback loop of IL-6 secretion and maintenance. Taken together, our results suggest that therapeutic approaches targeting cytokine receptors and adhesion molecules on cancer cells may potentially reduce metastatic load and improve current cancer treatments. [ABSTRACT FROM AUTHOR]

A necessary step in metastasis is the dissemination of malignant cells into the bloodstream, where cancer cells travel throughout the body as circulating tumor cells (CTC) in search of an opportunity to seed a secondary tumor. CTC represent a valuable diagnostic tool: evidence indicates that the quantity of CTC in the blood has been shown to relate to the severity of the illness, and samples are readily obtained through routine blood draws. As such, there has been a push toward developing technologies to reliably detect CTC using a variety of molecular and immunocytochemical techniques. In addition to their use in diagnostics, CTC detection systems that isolate CTC in such a way that the cells remain viable will allow for the performance of live-cell assays to facilitate the development of personalized cancer therapies. Moreover, techniques for the direct manipulation of CTC in circulation have been developed, intending to block metastasis in situ. We review a number of current and emerging micro- and nanobiotechnology approaches for the detection, capture, and manipulation of rare CTC aimed at advancing cancer treatment. WIREs Nanomed Nanobiotechnol 2012, 4:291-309. doi: 10.1002/wnan.168 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Presented is a review of our research on using macrocyclic bis-ureas as supramolecular building blocks. These macrocycles predictably self-assemble into columnar structures via strong urea-urea hydrogen bonds and pi-stacking interactions. We developed a facile synthetic route to these macrocyclic ureas, confirmed their self-assembly pattern, and are now assessing their potential as a supramolecular building block. A series of bis-urea macrocycles were synthesized and assembled to verify the fidelity of their self-assembly motifs. Ultimately, a large phenylether bis-urea macrocycle was synthesized that formed tubular assemblies containing a guest accessible channel. We have characterized the structure of the assembled nanotubes by NMR and X-ray crystallography and evaluated this new porous solid with respect to its binding properties and specificity. This porous self-assembled material is thermally and chemically stable and can reversibly bind and exchange a variety of guest molecules. [ABSTRACT FROM AUTHOR]

While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and refractory disease remain a significant therapeutic challenge. This is particularly true for patients with T-cell ALL and LBL, where survival for patients with relapsed/refractory disease remains dismal. Recent efforts to comprehensively profile the genomics of T-ALL/LBL to improve understanding of disease biology have enhanced our ability to identify high-risk patients at diagnosis who are more likely to relapse and have also identified novel targets for precision medicines. Novel immunotherapies have transformed the treatment landscape for patients with B-cell ALL (B-ALL). Many immunotherapies are under investigation in clinical trials for patients with T-ALL/LBL and early results are very promising. Given these insights into disease biology and the development of targeted and immune-based treatments, it is reasonable to hope for improved patient outcomes, although challenges still exist. In this review, we summarize the present state of understanding of the risk factors for relapse of T-ALL/LBL, established treatment regimens, and the promising small molecule inhibitors and immunotherapies with the potential to revolutionize the treatment of relapsed/refractory T-ALL/LBL.

The α-chemokine, stromal-derived factor-1 (SDF-1), has been linked to the homing of circulating tumor cells to bone. SDF-1 is expressed by bone microvascular cells and osteoblasts and normally functions to attract blood-borne hematopoietic stem and progenitor cells to marrow. It has been shown that treatment of cancer cells with soluble SDF-1 results in a more aggressive phenotype; however, the relevance of the administration of the soluble protein is unclear. As such, a flow device was functionalized with P-selectin and SDF-1 to mimic the bone marrow microvasculature and the initial steps of cell adhesion. The introduction of SDF-1 onto the adhesive surface was found to significantly enhance the adhesion of lymphoma cells, as well as low-density bone marrow cells (LDBMC), both in terms of the number of adherent cells and the strength of cell adhesion. Thus, SDF-1 has a synergistic effect with P-selectin on cancer cell adhesion and may be sufficient to promote preferential metastasis to bone.

A necessary step in metastasis is the dissemination of malignant cells into the bloodstream, where cancer cells travel throughout the body as circulating tumor cells (CTC) in search of an opportunity to seed a secondary tumor. CTC represent a valuable diagnostic tool: evidence indicates that the quantity of CTC in the blood has been shown to relate to the severity of the illness, and samples are readily obtained through routine blood draws. As such, there has been a push toward developing technologies to reliably detect CTC using a variety of molecular and immunocytochemical techniques. In addition to their use in diagnostics, CTC detection systems that isolate CTC in such a way that the cells remain viable will allow for the performance of live-cell assays to facilitate the development of personalized cancer therapies. Moreover, techniques for the direct manipulation of CTC in circulation have been developed, intending to block metastasis in situ. We review a number of current and emerging micro- and nanobiotechnology approaches for the detection, capture, and manipulation of rare CTC aimed at advancing cancer treatment., (Copyright © 2011 Wiley Periodicals, Inc.)

Herein we report a differential array of micelle-solubilized fluorophores for the detection and identification of small nitrated analytes, such as the explosives TNT, tetryl, RDX and HMX. The quenching ability of the analytes can be used to correlate their analyte identity, wherein the quenching patterns generated from the differential array are used in linear discriminant analysis (LDA). LDA results in a well-clustered two-dimensional plot, and a jack-knife analysis of the data suggests that this system can be used to identify unknown samples of analyte with 96 % accuracy and with a detection limit of 19 muM.