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The secreted growth factor Activin-A of the transforming growth factor β family and its receptors can promote or inhibit several cancer hallmarks including tumor cell proliferation and differentiation, vascularization, lymphangiogenesis and inflammation. However, a role in immune evasion and its relationship with tumor-induced muscle wasting and tumor vascularization, and the relative contributions of autocrine versus paracrine Activin signaling remain to be evaluated. To address this, we compared the effects of truncated soluble Activin receptor IIB as a ligand trap, or constitutively active mutant type IB receptor versus secreted Activin-A or the related ligand Nodal in mouse and human melanoma cell lines and tumor grafts. We found that although cell-autonomous receptor activation arrested tumor cell proliferation, Activin-A secretion stimulated melanoma cell dedifferentiation and tumor vascularization by functional blood vessels, and it increased primary and metastatic tumor burden and muscle wasting. Importantly, in mice with impaired adaptive immunity, the tumor-promoting effect of Activin-A was lost despite sustained vascularization and cachexia, suggesting that Activin-A promotes melanoma progression by inhibiting antitumor immunity. Paracrine Activin-A signaling emerges as a potential target for personalized therapies, both to reduce cachexia and to enhance the efficacy of immunotherapies., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Colloidal quantum dots (QDs) combined with a graphene charge transducer promise to provide a photoconducting platform with high quantum efficiency and large intrinsic gain, yet compatible with cost-efficient polymer substrates. The response time in these devices is limited, however, and fast switching is only possible by sacrificing the high sensitivity. Furthermore, tuning the QD size toward infrared absorption using conventional organic capping ligands progressively reduces the device performance characteristics. Here we demonstrate methods to couple large QDs (>6 nm in diameter) with organometal halide perovskites, enabling hybrid graphene phototransistor arrays on plastic foils that simultaneously exhibit a specific detectivity of 5 × 10 12 Jones and high video-frame-rate performance. PbI 2 and CH 3 NH 3 I co-mediated ligand exchange in PbS QDs improves surface passivation and facilitates electronic transport, yielding faster charge recovery, whereas PbS QDs embedded into a CH 3 NH 3 PbI 3 matrix produce spatially separated photocarriers leading to large gain.

We investigated the development of a topical indomethacin gel formulation of suitable consistency using Carbopol ETD 2001 as the gelling agent. Topical gel formulations containing 1% w/w indomethacin (IND), 1% w/w Carbopol ETD 2001 (C2001), 1% of trethanolamine (TEA), 30% hexylene glycol (HG) and 10% polyethylene glycol (PEG 300) were prepared with excipients Tween 80, PVP 25, both Tween 80 and PVP 25 or neither agent. These four gel formulations were tested after a period of 1 and 4 weeks at storage temperature of 6 degrees C, 20 +/- 2 degrees C and 45 degrees C. Physical evaluation of the stability of these gels was carried out by microscopic and rheological tests, measurement of pH and by visual inspection. Rheological properties were studied using the cone and plate method at shear rates of 600 to 6000 1/s. Viscosities corresponding to shear rates were also calculated. Our results indicated that C2001 could be used as a gelling agent for IND in topical preparations. IND-C2001 gels were clear and exhibited an acceptable appearance; gel behaviour was non-Newtonian and pseudoplastic. The addition of either Tween 80 or PVP 25 to the base gel formulation significantly increased the shear stresses and viscosity of the gels. These novel formulations exhibited good physical stability throughout the 4-week examination periods as inferred from pH measurements and microscopic examination. Additionally, the non-Newtonian pseudoplastic behaviour of the gels was maintained throughout storage, with only a minimal decrease in gel viscosity after 4 weeks. Differences in consistencies of the four formulations, although initially apparent, were no longer evident after 4 weeks of storage for all temperature conditions examined. Gels stored at high temperature (45 degrees C) developed a dark yellow color and decreased in viscosity compared to other storage temperature.

The stability of 20 topical gel formulations containing drug, 1% w/w indomethacin (IND), and 20% w/w Pluronic (PF-127) as a gel-forming agent, hexylene glycol (HG) and polyethylene glycol 300 (PEG) in different amounts (16, 20 and 24% w/w) as solvents and 1% w/w polyvinyl pyrrolidone (PVP, K-25) and Tween as excipients was determined by appearance and consistency of the gels, microscopy, pH and rheological measurements after 1 and 4 weeks storage, at 6 degrees C, 20 +/- 2 degrees C and 45 degrees C. Viscosity values were determined from rheograms by a Haake Rotovisco sensor at shear rates of 1000 to 10,000 l/s. The relationship between effectors (temperature and storage time) and response (viscosity) was determined using multiple regression analysis. All formulations were stable at room temperature (20 +/- 2 degrees C). The consistency of the gels containing HG and PEG decreased during storage at 6 degrees C. Storing the gels at 6 degrees C resulted in the precipitation of IND, but when PVP was incorporated into the IND-PF-127 gels, the stability of the gels was improved. All IND gels sustained their pseudoplastic flow behaviour. The viscosity decreased as storage time increased. A statistically significant model was obtained, showing that the effect of storage temperatures on the viscosity was much less than the effect of storage time.

Topical gel formulations containing a non-steroidal anti-inflammatory drug, indomethacin (IND), were prepared using 20% w/w Lutrol PF-127 as a gel-forming agent, and 16, 20 and 24% w/w Hexylene glycol (HG) or polyethylene glycol 300 (PEG) as solvents. 1% w/w Tween 80 and 1% w/w PVP 25 were added as excipients. The effects of the amounts of solvent and excipients on the physical characteristics of IND gel such as consistency, appearance, crystallization, pH and viscosity were studied. The results indicated that 1% w/w IND is able to form a structural gel. The viscosity values were calculated from the rheograms which were determined by a Haake Rotovisco sensor at a shear rate of 10,000 l/s. Viscosities corresponding to shear rates of 1000, 3000, 6000 and 9000 l/s were also calculated. Yield points were approximated from the rheograms. Although all IND gels maintained their pseudoplastic flow behaviour, their viscosities decreased markedly with increasing shear rates. Furthermore, increasing the amount of HG or PEG gave a more viscous gel except for the 24 w/w% HG gels which turned a jelly with or without either Tween or PVP. The difference in viscosities was explained by the changes in the gel compositions. 20% of PEG-1% PVP ranked first in viscosity followed by 16% PEG-1% PVP, 16% PEG-1% Tween, 24% PEG, 20% PEG-1% Tween and 16% HG-1% PVP. The results indicate that the excipients influence the physical characteristics of the gels. The optimum concentration for gels manifesting as strength of gel was 20% PEG in combination with 1% PVP which had the highest viscosity and yield value at a low shear rate.