Growth Analysis of Pulsed Laser Ablated Films

The spontaneous organization on a substrate of nanoparticles (NPs) nucleated in a laser-generated plasma results in self-assembling due to both direct specific interactions and to indirect ambient-mediated ones. A number of well-differentiated film morphologies are observed, from isolated NPs to percolated island structures. The distribution of the width of gaps between NPs, or islands formed upon NP coalescence in two representative percolated Au films, is lognormal, indicating that the growth process is random. A finer inspection of similar surface morphologies allows to correlate regularity in gap sizes and surface coverage to differences in film performance as substrates for surface-enhanced Raman spectroscopy.     

Antibody-based targeting of the tumor vasculature

Conventional cytotoxic therapies of cancer often suffer from a lack of specificity, leading to a poor therapeutic index and considerable toxicities to normal organs. An elegant way to overcome the disadvantages of conventional tumor therapy is the selective delivery of therapeutics to the tumor site by their conjugation to a carrier molecule specific for a tumor-associated molecular marker. Markers expressed on the tumor's vasculature represent particularly attractive targets for a site-specific pharmacodelivery due to their inherent accessibility for blood-borne agents and the various therapeutic options that they allow, ranging from intraluminal blood coagulation to the recruitment of immune cells. In this review, we will outline advances in the preclinical and clinical evaluation of antibody-based vascular targeting agents, describe technologies for the discovery of novel vascular targets and discuss future prospects for vascular targeting applications.     

Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment.

Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.     

Identification of monoclonal antibody defined epitopes on human leukocyte antigens utilizing phage display peptide libraries

Summary Utilizing phage display peptide libraries, we have identified and mapped the antigenic determinants recognized by mouse monoclonal antibodies (mAb) on two sets of immunologically important molecules, HLA class I and class II antigens. Anti-HLA class I mAb TP25.99 recognizes a conformational and a linear determinant on distinct regions of the HLA class I α3 domain. Anti-HLA class I mAb HO-4 recognizes a conformational determinant on the α2 domain of HLA-A2 and A28 allospecificities. Anti-HLA-DR1,-DR4,-DR6,-DR8,-DR9 mAb SM/549 recognizes a conformational determinant on the β chain of HLA class II antigens. These results indicate the versatility of phage display peptide libraries to characterize antigenic determinants recognized by anti-HLA mAb.     

Multiple biological responses activated by nuclear protein kinase C.

Protein kinase C is a family of serine-threonine kinases that are physiologically activated by a number of lipid cofactors and are important transducers in many agonist-induced signaling cascades. To date, 12 different isozymes of this kinase have been identified and are believed to play distinct regulatory roles. Protein kinase C was thought to reside in the cytosol in an inactive conformation and translocate to the plasma membrane upon cell activation by different stimuli. Nevertheless, a growing body of evidence has illustrated that this family of isozymes is capable of translocating to other cellular sites, including the nucleus. Moreover, it seems that some protein kinase C isoforms are resident within the nucleus. A wealth of data is being accumulated, demonstrating that nuclear protein kinase C isoforms are involved in the regulation of several critical biological functions such as cell proliferation and differentiation, neoplastic transformation, and apoptosis. In this review, we will discuss the most significant findings concerning nuclear protein kinase C which have been published during the past 5 years.