Characterization of the Primo-Vascular System in the Abdominal Cavity of Lung Cancer Mouse Model and Its Differences from the Lymphatic System

Cancer growth and dissemination have been extensively studied for a long time. Nevertheless, many new observations on anatomy and histopathology of cancer events are still reported such as formation of a vasculogenic-like network inside aggressive tumors. In this research, new kinds of micro-conduits, named primo-vessels, were found inside the abdominal cavity of NCI-H460 lung cancer murine xenograft models. These vascular threads were largely distributed on the surfaces of various organs and were often connected to peritoneal tumor nodules. Histological and immunofluorescent investigations showed that the primo-vessels had characteristic features that were distinctively different from those of similar-looking lymphatic vessels. They had multiple channels surrounded with loose collageneous matrices, which is in contrast to the single-channel structure of other vascular systems. The rod-shaped nuclei aligned longitudinally along the channels were assumed to be the endothelial cells of the primo-vessels, but LYVE-1, a specific marker of lymphatics, was not expressed, which indicates a clear difference from lymphatic endothelial cells. Taken together these findings on and characterization of the novel threadlike vascular structures in cancer models may have important implications for cancer prognosis and for therapy

Experimental assessment of pro-lymphangiogenic growth factors in the treatment of post-surgical lymphedema following lymphadenectomy

Introduction: Lymphedema is a frequent consequence of lymph node excision during breast cancer surgery. Current treatment options are limited mainly to external compression therapies to limit edema development. We investigated previously, postsurgical lymphedema in a sheep model following the removal of a single lymph node and determined that autologous lymph node transplantation has the potential to reduce or prevent edema development. In this report, we examine the potential of lymphangiogenic therapy to restore lymphatic function and reduce postsurgical lymphedema. Methods: Lymphangiogenic growth factors (vascular endothelial growth factor C (VEGF-C)) and angiopoietin-2 (ANG-2) were loaded into a gel-based drug delivery system (HAMC; a blend of hyaluronan and methylcellulose). Drug release rates and lymphangiogenic signaling in target endothelial cells were assessed in vitro and vascular permeability biocompatibility tests were examined in vivo. Following, the removal of a single popliteal lymph node, HAMC with the growth factors was injected into the excision site. Six weeks later, lymphatic functionality was assessed by injecting 125Iodine radiolabeled bovine serum albumin (125I-BSA) into prenodal vessels and measuring its recovery in plasma. Circumferential leg measurements were plotted over time and areas under the curves used to quantify edema formation. Results: The growth factors were released over a two-week period in vitro by diffusion from HAMC, with 50% being released in the first 24 hr. The system induced lymphangiogenic signaling in target endothelial cells, while inducing only a minimal inflammatory response in sheep. Removal of the node significantly reduced lymphatic functionality (nodectomy 1.9 ± 0.9, HAMC alone 1.7 ± 0.8) compared with intact groups (3.2 ± 0.7). In contrast, there was no significant difference between the growth factor treatment group (2.3 ± 0.73) and the intact group indicating improved function with the molecular factors. An increase in the number of regenerated lymphatic vessels at treatment sites was observed with fluoroscopy. Groups receiving HAMC plus growth factors displayed significantly reduced edema (107.4 ± 51.3) compared with nontreated groups (nodectomy 219.8 ± 118.7 and HAMC alone 162.6 ± 141). Conclusions: Growth factor therapy has the potential to increase lymphatic function and reduce edema magnitude in an animal model of lymphedema. The application of this concept to lymphedema patients warrants further examination

Population Genomics of Parallel Adaptation in Threespine Stickleback using Sequenced RAD Tags

Next-generation sequencing technology provides novel opportunities for gathering genome-scale sequence data in natural populations, laying the empirical foundation for the evolving field of population genomics. Here we conducted a genome scan of nucleotide diversity and differentiation in natural populations of threespine stickleback (Gasterosteus aculeatus). We used Illumina-sequenced RAD tags to identify and type over 45,000 single nucleotide polymorphisms (SNPs) in each of 100 individuals from two oceanic and three freshwater populations. Overall estimates of genetic diversity and differentiation among populations confirm the biogeographic hypothesis that large panmictic oceanic populations have repeatedly given rise to phenotypically divergent freshwater populations. Genomic regions exhibiting signatures of both balancing and divergent selection were remarkably consistent across multiple, independently derived populations, indicating that replicate parallel phenotypic evolution in stickleback may be occurring through extensive, parallel genetic evolution at a genome-wide scale. Some of these genomic regions co-localize with previously identified QTL for stickleback phenotypic variation identified using laboratory mapping crosses. In addition, we have identified several novel regions showing parallel differentiation across independent populations. Annotation of these regions revealed numerous genes that are candidates for stickleback phenotypic evolution and will form the basis of future genetic analyses in this and other organisms. This study represents the first high-density SNP–based genome scan of genetic diversity and differentiation for populations of threespine stickleback in the wild. These data illustrate the complementary nature of laboratory crosses and population genomic scans by confirming the adaptive significance of previously identified genomic regions, elucidating the particular evolutionary and demographic history of such regions in natural populations, and identifying new genomic regions and candidate genes of evolutionary significance

Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses

CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens

Preventive dentistry for the general dental practitioner

Although the prevalence of dental caries has decreased gradually in the past three decades in the Australian population, dental caries remains the primary reason for tooth loss in Australia. At the community level, total health expenditure on the treatment of dental caries (and its consequences) is substantial, Accordingly, caries prevention is an important focus at both the individual and community levels. This paper outlines the principles upon which modern caries prevention is based and stresses the importance of manipulating the oral environment (in terms of salivary parameters, ions, pH and the oral flora) as a major strategy for effective long-term caries prevention. Practical advice is provided on the correct home use of preventive agents, including chewing gums, chlorhexidine, fluorides, bicarbonate rinses and phosphopeptides