M402, a Novel Heparan Sulfate Mimetic, Targets Multiple Pathways Implicated in Tumor Progression and Metastasis

Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis

Behaviour of Coconut Mites Preceding Take-off to Passive Aerial Dispersal

For more than three decades the coconut mite Aceria guerreronis Keifer is one of the most important pests of coconut palms and has recently spread to many coconut production areas worldwide. Colonization of coconut palms is thought to arise from mites dispersing aerially after take-off from other plants within the same plantation or other plantations. The underlying dispersal behaviour of the mite at take-off, in the airborne state and after landing is largely unknown and this is essential to understand how they spread from tree to tree. In this article we studied whether take-off to aerial dispersal of coconut mites is preceded by characteristic behaviour, whether there is a correlation between the body position preceding aerial dispersal and the direction of the wind, and whether the substrate (outer surface of coconut bracts or epidermis) and the wind speed matter to the decision to take-off. We found that take-off can sometimes be preceded by a raised body stance, but more frequently take-off occurs while the mite is walking or resting on its substrate. Coconut mites that become airborne assumed a body stance that had no relation to the wind direction. Take-off was suppressed on a substrate providing food to coconut mites, but occurred significantly more frequently on the outer surface of coconut bracts than on the surface of the fruit. For both substrates, take-off frequency increased with wind speed. We conclude that coconut mites have at least some degree of control over take-off for aerial dispersal and that there is as yet no reason to infer that a raised body stance is necessary to become airborne

Yeast Biofilms

Yeast biofilms are an escalating clinical problem, which affect both the healthy and immunocompromised, and are related to significant rates of mortality within hospitalized patients. Candida albicans is the most notorious yeast biofilm former and as a result the most widely studied; however, other Candida species and yeasts such as Cryptococcus neoformans are also implicated in biofilm-associated infections. Yeast biofilms have distinct developmental phases, including adhesion, colonization, maturation and dispersal, which have been examined utilizing various in vitro and in vivo model systems. Furthermore, the complex molecular events governing biofilm development are slowly being elucidated, including the role of quorum sensing. Clinically, biofilms act as reservoirs for systemic infection, and also induce localized pathology and tissue damage. However, the key virulence factor is their recalcitrance to antifungal therapy. This chapter will discuss our current understanding of the role that yeast biofilms play in the clinical setting