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Email: uh. This article has been cited by other articles in PMC. Abstract The development of peripheral lymphoid tissues from the mesoderm is the result of a complex convergence combining lymphohematopoietic differentiation with the local specification of nonhematopoietic mesenchymal components. Although the various transcriptional regulators with fate-determining effects in diversifying the mobile leukocyte subsets have been thoroughly studied and identified, the tissue-specific determinants promoting the regional differentiation of resident mesenchyme are less understood.

Of these factors, various members of the NK-class Nkx paralogues have emerged as key regulators for the organogenesis of spleen and mucosal lymphoid tissues, and recent data have also indicated their involvement in various pathological events, including gut inflammation and hematopoietic malignancies.

Int J Mol Sci. Published online Jan 8. Copyright © by the authors. This article has been cited by other articles in PMC.

Here, we summarize available data on the roles of Nkx in lymphoid tissue development and discuss its possible value as a developmental marker and disease-associated pathogenic trait. Keywords: Nkx, lymphoid organs, lymphoma, inflammation Introduction: Roles of Nkx Family Members in Cellular Differentiation and Organogenesis—A General Overview The development of complex organisms such as the mammalian body requires a highly regulated coordination of gene expression.

Homeobox genes containing helix-turn-helix DNA-binding motif first described in Drosophila are master regulators of developmental processes such as mesodermal patterning.

The hormone-sensitive cells die and the hormone-resistant cells overgrow, resulting in disease progression. The drug of choice for secondary treatment is estramustine Estracyt. The success of the therapy is followed by changes of the prostate-specific antigen level and Karnofsky scale.

The largest group of homeobox genes comprises the HOX including the extended HOX class of transcription factors, which may be phylogenetically related to the NK class of homeobox genes that constitutes the second largest group of homeobox-encoding genes.

Two NK-2 class genes, namely, tinman and bagpipe, are responsible for dorsal heart tube formation, mesodermal differentiation, and development of gut musculature, respectively.

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They are able to activate signaling pathways responsible for cell differentiation, migration, and maturation, thus their activity is essential to the formation and maintenance of a normally structured and functioning organism. This complexity is well illustrated by the multiple roles of the NK-2 class members.

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They are necessary for the development of spinal cord V3 interneurons and hindbrain visceral motor neurons, as the spinal cords of mice lacking these factors have reduced number of V3 neurons and expanded motor neurons. This compensation is probably related to the ectopic expression of Nkx2. Although the various NK-2 homologues have different sequences reflecting different functions, they display overlapping homeodomain structure and DNA-sequence specificities as defined by its first helical region and carboxy-terminal region and often overlapping expression patterns.

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The spleen, the largest peripheral lymphoid organ, develops following signals originating from the splanchnic mesodermal plate SMP during embryonic development, 21 a transient structure expressing Nkx also known as Bapx1.

The Nkx—producing SMP has an essential role in the formation of left-right asymmetry 21 and the development of spleen from E The absence of this factor causes asplenia and disturbed pyloric sphincter formation due to impairments of the visceral mesoderm.

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As SMP formation is permitted in the absence of Nkx, it is likely that this factor is not necessary for the appearance of SMP but is required for its maturation to provide further factors promoting spleen development. Another Nkx member, Nkx, is also expressed in the developing spleen and its absence also leads to asplenia.

Nkx is expressed in specified splenic mesenchymal cells which will form the splenic anlage. Nkx is expressed in the spleen, pathology of prostate cancer ncbi, hindgut, and pharyngeal endoderm.

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MAdCAM-1 has a crucial role in lymphocyte homing to mucosal tissues by binding integrin α4β7 and L-selectin leukocyte homing receptors.

The absence of Nkx also disrupts the architecture of marginal sinus, including the organization of marginal zone MZ macrophage subpopulations and MAdCAM-1—positive marginal sinus-lining endothelial cells, similar to the deficiency of lymphotoxin β receptor LTβR ; however, the RP vasculature is unperturbed in the absence of LTβR.

The MZ is affected in both conditions.

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Activation of this endothelial layer by bacterial and other agents results in the upregulation of adhesion molecules and chemokines necessary for the vascular attachment and migration of leukocytes. Altered expression of endothelial markers such as Nkx and its potential target MAdCAM-1 can cause a perturbation in leukocyte traffic and inflammatory response.

Consequently, the development of inflammatory bowel diseases IBD such as Crohn disease CD and ulcerative colitis UC can be linked to these endothelial factors. According to Xiao et al, single-nucleotide polymorphisms of Nkx namely, pathology of prostate cancer ncbi and rs are associated with CD and UC.

Polymorphism rs may contribute significantly to the emergence of both CD and UC, whereas occurrence of the T allele of rs can increase the risk of CD. Tumor necrosis factor α can further augment adhesion molecule expression in the intestines and it may crossregulate the genes affected by Nkx This cell line was originated from a patient with CD and showed downregulation Prosztata erős fájdalom 33 and upregulation of 92 genes following Nkx knockdown.

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Intriguingly, Nkx expression not only distinguished intestinal myofibroblasts from skin fibroblasts but it also turned out to be a determinant in the preservation of myofibroblast identity, presumably involved in regulating colonic stem cell niche. The exact connection between the Nkx2.

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The lineage-specific expression of Nkx has not been formally defined yet either in humans or in mice. Using a recently developed and validated immunohistochemistry-grade anti-human Nkx mAb 3145 may in the future enable a conclusive assessment to be achieved, even though its expression is probably shared by several mesenchymal cells in a regionally restricted manner of the colonic subepithelial connective tissue Figure 1.

DOI: Bevezetés: Az utóbbi években az oligometastaticus prosztatadaganatok kezelése során a szisztémás kezelés mellett egyre gyakrabban végzik a primer tumor lokális kezelését is.