Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components

Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates’ therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers

Morphometric study of the mare oviductal mucosa at different reproductive stages

The objectives of this work were to describe some morphometric characteristics and to establish quantitative parameters of different regions of the equine oviductal mucosa from the isthmus, ampullary-isthmic junction (AIJ), and ampulla. Twenty-one mixed-bred mares were used for this study. Mares were selected in the following reproductive phases: anestrus, estrus, and diestrus. The left oviducts were examined with light microscopy, and rights ones were studied through the intraoviductal molds. The isthmus showed the smallest luminal area, mucosal area, epithelial perimeter, and luminal diameter. On the molds surfaces, some grooves extended as longitudinal canals, reducing their depth as they approached to the AIJ. Several small height projections, some obliquely positioned towards utero-tubal junction, were observed in all reproductive phases. These formations may represent pockets or cul-de-sacs in the basal areas of the epithelial folds. The AIJ mucosa gradually changed from the smooth isthmic region toward highly folded ampulla. The number and complexity of epithelial folds showed moderate increase in the same way that many of the morphometric parameters. Multiple curves were observed on the molds of the AIJ, creating a zigzag path in the oviductal lumen. In the ampulla, the high branched epithelial folds occupied most of the lumen, leaving a small luminal area free. A linear relationship between epithelial perimeter and mucosal area was found. The presence of glandular-like structures was observed in all the reproductive stages studied. The equine endosalpinx reveals a highly complex tridimensional arrangement where each region shows very particular and specific designs.Fil: Mouguelar, Horacio. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Díaz, Tomás. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Borghi, Damiana. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Rolando Javier, Quinteros. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Bonino, Facundo Ubaldo. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria; ArgentinaFil: Apichela, Silvana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Aguilar, José Javier. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Producción Animal; Argentin