Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

On neutron stars in ƒ (R) theories: Small radii, large masses and large energy emitted in a merger

In the context of ƒ (R) gravity theories, we show that the apparent mass of a neutron star as seen from an observer at infinity is numerically calculable but requires careful matching, first at the star’s edge, between interior and exterior solutions, none of them being totally Schwarzschild-like but presenting instead small oscillations of the curvature scalar R; and second at large radii, where the Newtonian potential is used to identify the mass of the neutron star. We find that for the same equation of state, this mass definition is always larger than its general relativistic counterpart. We exemplify this with quadratic R^2 and Hu-Sawicki-like modifications of the standard General Relativity action. Therefore, the finding of two-solar mass neutron stars basically imposes no constraint on stable ƒ (R) theories. However, star radii are in general smaller than in General Relativity, which can give an observational handle on such classes of models at the astrophysical level. Both larger masses and smaller matter radii are due to much of the apparent effective energy residing in the outer metric for scalar-tensor theories. Finally, because the ƒ (R) neutron star masses can be much larger than General Relativity counterparts, the total energy available for radiating gravitational waves could be of order several solar masses, and thus a merger of these stars constitutes an interesting wave source.