These results suggest that a subset of ALK-negative IMTs have rearrangement of ROS1, ETV6 or NTRK3 as a possible oncogenic mechanism, and that the detection of these alterations may be of diagnostic value and helpful for determining promising therapeutic strategies.

Some markers of angiogenic endothelial cells are emerging as targets for cancer therapy. The present study compared the expression of CD105 with that of other endothelial markers in cancers from various organs. Surgically resected cancer tissues from 188 patients comprising brain (n = 17), lung (n = 38), breast (n = 30), stomach (n = 30), colon (n = 31), liver (n = 32), and kidney (n = 10) cancers were immunohistochemically analyzed on tissue microarrays using a panel of eight endothelial markers. CD31 was expressed in vascular endothelial cells in cancer lesions as well as in non-cancerous areas (30-100%) in all core tissue samples. CD105 expression was intense and restricted to capillary endothelial cells in cancer lesions (>73%). In contrast, positive expression of CD105 was seen in <20% of non-cancerous areas in the same organs. However, no significant difference in CD105 expression in vascular endothelial cells between cancer lesions and non-cancerous areas from liver and renal cancer samples was found. Vascular endothelial growth factor (VEGF), Flt1, and Flk1 were also expressed, but only sporadically and in few samples (<30%), and transforming growth factor (TGF)-beta1 and TGF-betaRII were negative in vascular endothelial cells but generally positive in cancer cells. CD44 was strongly expressed in sinusoidal endothelial cells of the liver (90-100%). These results show that CD105 is expressed specifically in the tumor angiogenesis of brain, lung, breast, stomach, and colon cancers.

In the past few years, a number of microneedle designs have been proposed for transdermal drug delivery of high molecular weight drugs. However, most of them do not increase the drug permeability in skin significantly. In other cases, designs developed based on certain criteria (e.g. strength of the microneedles) have failed to meet other criteria (e.g. drug permeability in skin, throughputs of the drugs, etc.). It is obvious therefore that in order to determine the 'optimum' design of these microneedles, the effect of different factors (e.g. length of the microneedle, surface area of the patch, etc.) along with various transport properties of drug transport behaviour using microneedles should be determined accurately. Appropriate mathematical models for drug transport from these systems into skin have the potential to resolve some of these issues. To address this, a parametric analysis for transdermal delivery of a high molecular weight drug from a microneedle is presented in this paper. The simulations have allowed us to identify the significance of various factors that influence the drug delivery while designing microneedle arrays. A scaling analysis is also done which shows the functional dependence of drug concentration on other variables of skin and microneedle arrays.

Heparin is a widely used clinical anticoagulant. It is also a linear glycosaminoglycan with an average mass between 10 and 20 kDa and is primarily made up of trisulfated disaccharides comprised of 1,4-linked iduronic acid and glucosamine residues containing some glucuronic acid residues. Heparin is biosynthesized in the Golgi of mast cells commonly found in the liver, intestines, and lungs. Pharmaceutical heparin currently used in the United States is primarily extracted from porcine intestines. Other sources of heparin including bovine intestine and bovine lung are being examined as potential substitutes for porcine intestinal heparin. These additional sources are intended to serve to diversify the heparin supply, making this lifesaving drug more secure. The current study examines bovine heparins prepared from both intestines and lung and compares these to porcine intestinal heparin. The structural properties of these heparins are examined using nuclear magnetic resonance, gel permeation chromatography, and disaccharide analysis of heparinase-catalyzed depolymerized heparin. The in vitro functional activities of these heparins have also been determined. The goal of this study is to establish the structural and functional similarities and potential differences between bovine and porcine heparins. Porcine and bovine heparins have structural and compositional similarities and differences.

Novel nitrogenous diterpenoids, spongolactams A-C (1-3), were isolated as trace components of an Okinawan marine sponge, Spongia sp., by an LC/MS-guided assay for farnesyl transferase (FTase) inhibitors. Their structures were elucidated by spectroscopic analyses. To evaluate their structures and biological activity, the metabolites were semisynthesized from the known furanoditerpene 5, obtained from the same sponge. Three related compounds 4, 13, and 16 were also semisynthesized. The IC50 values against FTase for 1-3 were 23, 130, and >260 microM, respectively, while the IC50 values against a human tumor cell line were 2.0, 3.5, and 20 microM, respectively. The structure-activity relationships within the six compounds suggest some positive correlation between FTase inhibitory and cytotoxic activities.