Since classical Hodgkin's lymphoma (cHL) is characterised by abnormalities in the apoptotic pathways, apoptosis may play a central role in its pathogenesis. In conclusion, both HDACi treatments diminished the inherent tumorigenic growth potential of the tumor embryonal source, although Trichostatin A did not diminish the potentially dangerous expression of cancer-related genes and the amount of CSCLC.Īpoptosis is a type of programmed cell death (PCD) with specific morphologic changes in the dying cell. Valproate decreased the amount of CSCLCs, and downregulated the expressions of pluripotency/stemness and differentiation genes. Trichostatin A increased the amount of CSCLCs, and upregulated the mRNA expression of pluripotency/stemness genes as well as differentiation genes, e.g., T and Eomes. Both HDACi treatments of the embryos-proper significantly reduced teratoma growth, although this could be related neither to apoptosis nor proliferation. Mitotic indices were higher than apoptotic indices in both components. For the first time, within teratomas, we histopathologically assessed the undifferentiated component containing cancer stem cell-like cells (CSCLCs) and differentiated components containing numerous lymphocytes.
The growth of teratomas was measured for seven days, and histopathological analysis, IHC/morphometry quantification, gene enrichment analysis, and qPCR analysis on a selected panel of pluripotency and early differentiation genes followed. Our aim was to investigate the impact of histone deacetylase inhibitors (HDACi) on the in vitro growth of experimental mouse teratoma by treating their embryonic source, the embryo-proper, composed only of the three germ layers.
Expression of these indices as a mitotic-apoptotic ratio, e.g., 1:1, 1:2, 2:1, etc., may better reflect the growth potential of the examined, usually tumor tissue than determination of the mitotic index alone.Īmong testicular germ cell tumors, teratomas may often be very aggressive and therapy-resistant. Thus, we believe that each pathologist should be professionally obliged to determine apoptotic index when assessing mitotic index. Of course, the method is not absolutely accurate (the sophisticated and expensive methods mentioned above are not so either), but it is rapid and inexpensive. During more than 25 years of research into apoptosis, the Zagreb Group for the Study of Apoptosis (Apoptosis Section, Department of Basic Medical Sciences, Academy of Medical Sciences of Croatia) have found it possible to determine the number of apoptotic cells and apoptotic bodies (apoptotic index) in daily routine on classic HE stained histologic slides by counting in 10 large fields under light microscope, following the methodology of mitotic index determination. It is known that, unlike necrosis, there is no inflammatory reaction in the vicinity of apoptotic cells and apoptotic bodies. Apoptotic bodies are fragments of the disintegrated apoptotic cell and each fragment of dense cytoplasm usually contains a fragment of disintegrated nucleus. As a rule, apoptotic cell has a shrunken, condensed, dark red cytoplasm and dark purple picnotic nucleus, and is surrounded by light, 'hollow' space (halo). It is well known that the basic morphological characteristics of apoptotic cells and apoptotic bodies have been described on the basis of classic light microscopy of histologic hemalaun-eosin (HE) stained slides. Reading off the results obtained by these methods is mostly left to investigators inexperienced in morphological analysis. Irrespective of considerable technical improvements, these methods are associated with a relatively high rate of false-positive and false-negative results. These methods are quite demanding and time consuming, e.g., TUNEL, flow cytometry and its modifications, immunohistochemistry, hybridization in situ, etc. Stimulated by the huge scientific interest in programmed cell death, the sophisticated but expensive methods of apoptosis detection, occasionally even in various stages of the apoptotic process, have been developed in the last two decades.
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