Rett syndrome (RTT, MIM No. 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as an X-linked dominant trait, therefore almost exclusively affecting females. About 80% of RTT cases are sporadic caused by mutations in the MECP2 gene located on Xq28. The gene codes for two isoforms of the methyl-CpG-binding protein (MeCP2, MeCP2B) which are involved in transcriptional silencing through DNA methylation. The gene has 4 exons. The fourth one is the largest. Almost all mutations in MECP2 occur de novo. Although mutations are dispersed throughout the gene, about 67% of all MECP2 mutations, caused by C>T transitions at 8 CpG dinucleotides, are located in the third and fourth exon. The most common mutation is R168X. So far, there is no clear evidence on genotype-phenotype correlations. There are also reports claiming that the same mutation can provoke different phenotypes. It was shown that MeCP2 can silence certain genes. One of them, brain-derived neurotrophic factor, is essential for neural plasticity, learning and memory. This discovery revealed the role of MeCP2 in the control of neuronal activity-dependent gene regulation and suggested that the pathology of RTT may result from deregulation of this process.

No abstract

No abstract

The function of the Toll-like receptor (TLR) family members has been extensively studied in the recent decades. The TLR family is generally involved in the defense against microbial infections. TLRs are expressed mainly on macrophages and dendritic cells (DCs) and activate these cells upon ligand binding. The activation of TLRs basically initiates innate immune response, but can also induce adaptive immune response. TLRs have also been found on epithelial and tumor cells, but their role on tumor cells is still unclear. In some tumor types TLRs promote tumor proliferation and survival, while in others TLR2, -3 and -9 have been shown to be directly involved in apoptosis. Therefore, they seem to be promising candidates for the development of new, effective therapeutic options. It is however necessary to conduct comprehensive studies to assess the significance of these receptors in neoplastic cells. TLR ligands can also be used as immunostimulatory molecules to boost immune system in anticancer treatment. In this respect TLRs have been used in numerous preclinical and clinical studies. However, adjuvants can evoke distinct immune responses, either beneficial or deleterious in the neoplastic setting. Moreover, neoplastic processes may also subvert different signaling pathways and thereby advance cancer progression. From both points of view careful selection of adjuvants is a necessary prerequisite for cancer patient's treatment. Thus, TLRs have a dual role, when used as a target for immunostimulation, as well as when used directly to kill the cancer cell.

Toll‐like receptor 3 (TLR3) is a member of Toll‐like receptors who recognize structurally conserved molecules derived from pathogens and trigger the immune response. To clarify if TLR3, is expressed in certain tumour cell lines and whether it is functional and what is the response of these cell lines to different concentrations of poly I:C treatment, we have screened SW480, SW620, FaDu and Detroit 562 cell lines using real‐time PCR, flow cytometry and ELISA. We have shown that all these cell lines express TLR3 on mRNA and protein level but it is only functional in Detroit 562 cell line since only in these cells poly I:C treatment triggered the IL‐6 secretion. In addition, poly I:C treatment inhibited cell growth and triggered up‐regulation of IL‐12p40, IL‐8 and Il‐1α in Detroit 562 cell line. By using annexin‐V apoptosis detection kit, we have found that poly I:C triggers apoptosis in Detroit 562 cell line. We have found here that based on the results of TLR3 functionality there is a huge difference between FaDu and Detroit 562 cell lines which are of the same origin (pharynx) but FaDu is primary and Detroit 562 metastatic carcinoma. Our study also shows that Detroit 562 cell line could be a good model for cancer therapy research and development as it is responsive to TLR3 agonists which consequently drives it to apoptosis.