Возможность прогнозирования клеточного типа увеальных меланом без использования инвазивных методов диагностики

Резюме. С помощью дискриминантного анализа установлена возможность определения клеточного типа меланомы увеального тракта в процессе проведения комбинированного (фотокоагуляция + брахитерапия) лечения. Разработана высокозначимая (l = 0,08; р = 0,002) дискриминантная модель, включающая ряд клинических (степень пигментации, пол, скорость роста меланомы) и иммунологических (количество Т- и В-лимфоцитов, процент Т-хелперов и др.) показателей. Особое место в модели занимают признаки, в наибольшей степени отражающие биологические особенности увеальных меланом различного клеточного состава, а именно — скорость изменения размера опухоли в процессе лечения и изменение показателей клеточного иммунитета. Ключевые слова: увеальная меланома, клеточный тип, клинико-морфологические, иммунологические показатели, дискриминантный анализ.Summary. Application of the discriminant analysis shows that it is possible to define the cell type of melanoma of uveal tract of the eye in the process of combined (photocoagulation + brachytherapy) treatment. A highly reliable (l= 0,08; р = 0,002) discriminant model was elaborated, involving a number of both clinical (pigmentation level, gender, melanoma growth rate) and immunological (number of T and B lymphocytes, T helper rate, etc.) indicators. In this model, especially important are those traits that most pronouncedly reflect the biological peculiarities of uveal melanomas of various cellular compositions, namely — the pace of tumor size growth in the process of treatment and changes in cell immunity indicators. Key Words: uveal melanoma, cell type, clinical and morphological, immunological indicators, discriminant analysis

Dissecting the Wnt secretion pathway: key questions on the modification and intracellular trafficking of Wnt proteins

The Wnt family of signalling proteins has essential functions in development and adult tissue homoeostasis throughout the animal kingdom. Although signalling cascades triggered by Wnt proteins have been extensively studied, much remains to be learned about how Wnts are produced and secreted. Over the past few years, it has become clear that the secretion of Wnt proteins requires a specialized trafficking pathway. As this pathway has been discussed in two recent reviews (Lorenowicz & Korswagen 2009, Port & Basler 2010), we will focus our discussion on the key questions that need to be addressed to gain a more complete understanding of the mechanism and regulation of this essential secretion pathway

Sorting nexins provide diversity for retromer-dependent trafficking events

Sorting nexins are a large family of evolutionarily conserved phosphoinositide-binding proteins that have fundamental roles in orchestrating cargo sorting through the membranous maze that is the endosomal network. One ancient group of complexes that contain sorting nexins is the retromer. Here we discuss how retromer complexes regulate endosomal sorting, and describe how this is generating exciting new insight into the central role played by endosomal sorting in development and homeostasis of normal tissues

Sailing with the Wnt: charting the Wnt processing and secretion route

Wnt proteins are members of a highly conserved family of signalling molecules that play a central role in development and disease. During the past years, the different signalling pathways that are triggered by Wnt proteins have been studied in detail, but it is still largely unknown how a functional Wnt protein is produced and secreted. The recent finding that Wnt proteins are post-translationally modified and the discovery of the Wnt binding protein Wntless and its trafficking by the retromer complex show that Wnt secretion is a complex and highly regulated process. In this review, we will give an overview of the Wnt maturation and secretion pathway and discuss how this process may influence the spreading and signalling activity of Wnt

Sailing with the Wnt: charting the Wnt processing and secretion route

Wnt proteins are members of a highly conserved family of signalling molecules that play a central role in development and disease. During the past years, the different signalling pathways that are triggered by Wnt proteins have been studied in detail, but it is still largely unknown how a functional Wnt protein is produced and secreted. The recent finding that Wnt proteins are post-translationally modified and the discovery of the Wnt binding protein Wntless and its trafficking by the retromer complex show that Wnt secretion is a complex and highly regulated process. In this review, we will give an overview of the Wnt maturation and secretion pathway and discuss how this process may influence the spreading and signalling activity of Wnt.

Wnt signaling requires retromer-dependent recycling of MIG-14/Wntless in Wnt-producing cells.

Wnt proteins are secreted signaling molecules that play a central role in development and adult tissue homeostasis. We have previously shown that Wnt signaling requires retromer function in Wnt-producing cells. The retromer is a multiprotein complex that mediates endosome-to-Golgi transport of specific sorting receptors. MIG-14/Wls is a conserved transmembrane protein that binds Wnt and is required in Wnt-producing cells for Wnt secretion. Here, we demonstrate that in the absence of retromer function, MIG-14/Wls is degraded in lysosomes and becomes limiting for Wnt signaling. We show that retromer-dependent recycling of MIG-14/Wls is part of a trafficking pathway that retrieves MIG-14/Wls from the plasma membrane. We propose that MIG-14/Wls cycles between the Golgi and the plasma membrane to mediate Wnt secretion. Regulation of this transport pathway may enable Wnt-producing cells to control the range of Wnt signaling in the tissue