Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer

Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45S rDNA promoter. However, the DNA methylation state of the 45S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18S, 28S, 5.8S and 45S external transcribed spacer (45S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation between spliced rRNA expression levels, possibly due to changes in rRNA processing, which requires further investigation

Gene and Cell Therapies Overview Under the Light of Health Economics

With the increase in drug development studies for rare diseases, gene therapies have recently come to the fore more frequently. In addition to orphan drugs used in the treatment of rare diseases, advanced therapy medicinal products have been developed. Advanced therapy medicinal products are a fast-growing field. Although it is not a treatment method used only in the field of rare diseases, it is also used in the fields of oncology and cardiovascular diseases, musculoskeletal diseases. Regenerative medicine can be promising in cases where advanced therapy medicinal products are difficult and clinically uncertain. There are various cell therapies related to regenerative medicine and cell-based therapies are one of them. Gene therapies, cell-based therapies, advanced therapy medicinal products and regenerative medicine products have high producer price and high production cost. Because all these treatments have limited clinical evidence and high costs, they are difficult to evaluate in terms of health technology assessment (HTA), and special considerations are needed for evaluation. As a solution, costs should be limited and clinical developments should be provided in cooperation with the society. SAVE (equivalent to young life saved) is recommended to evaluate the lifetime health profiles of curative treatments such as gene therapies. In order to reduce the budgetary burden of gene therapies, outcome-directed entry agreements with income-based payments are recommended. Compulsory use of gene therapies and non-reimbursement of these drugs can lead to catastrophic health expenditures. Various payment methods are offered to avoid catastrophic health expenditures. Income-based payment and outcome-based payment are some of these methods. It is also advocated that high prices should be accepted by the society, since gene therapies to be applied in the treatment of rare diseases will be applied to a small population. Both the support of the society to accept the high price of gene therapies, the support of the producer and the support of the payer are important in the development of gene therapies and their supply to the market

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Tables not included in the main manuscript have been listed. Table S1. Number of probe sets affected by AZA treatment; Table S2. Comparison of significantly altered probe sets with the independent study GSE20713 Dataset; Table S3. Cancer vs. normal analysis of TAGLN mRNA in Oncomine database. (PDF 18 kb

Constraints on North Anatolian Fault Zone Width in the Crust and Upper Mantle From S Wave Teleseismic Tomography

We present high-resolution S wave teleseismic tomography images of the western segment of the North Anatolian Fault Zone (NAFZ) in Turkey using teleseismic data recorded during the deployment period of the Dense Array for Northern Anatolia array. The array comprised 66 stations with a nominal station spacing of 7 km, thus permitting a horizontal and vertical resolution of approximately 15 km. We use the current S wave results with previously published P wave teleseismic tomography to produce maps of relative VP/VSanomalies, which we use to highlight the difference in overall composition of the three terranes separated by the northern (NNAF) and southern branches of the NAFZ. Our results show a narrow S wave low-velocity anomaly beneath the northern branch of the NAFZ extending from the upper crust, where it has a width of ∼10 km, to the lower crust, where it widens to ∼30 km. This low-velocity zone most likely extends into the upper mantle, where we constrain its width to be ≤ 50 km and interpret it as indicative of localized shear beneath the NNAF; this structure is similar to what has been observed for the NAFZ west of 32°, and therefore, we propose that the structure of the NNAF is similar to that of the NAFZ in the east. The southern branch of the NAFZ does not show a very strong signature in our images, and we conclude that it is most likely rooted in the crust, possibly accommodating deformation related to rotation of the Armutlu/Almacik Blocks situated between the two NAFZ branches

A Market Research Of Obesity And Bariatric Surgery In Turkey And Tunisia

This article aims to discuss four topics according to the recent scientific data a) to overview the frequency of obese and overweight individuals among Tunisia and Turkey populations; b) to examine health technology assessment of bariatric surgery (BS) report (HTA) in Tunisia and Turkey; c) to evaluate the cost and cost reimbursements by social health systems for bariatric surgery in Turkey and Tunisia; d) to examine the total number of bariatric surgical procedures and their costs in state and private health organizations in Tunisia and Turkey. The OECD (2011-2017) Turkey report was included for the data for the frequency of obese and over-weighted people among the general population Turkey, while the WHO report of «Diabetes Prevalence and Diabetes Risk Factors» of 2016 was included for Tunisia

Seismic tomography of the North Anatolian Fault: New insights into structural heterogeneity along a continental strike-slip fault

Knowledge of the structure of continental strike-slip faults within the lithosphere is essential to understand where the deformation occurs and how strain localizes with depth. With the aim to improve the constraints on the lower crust and upper mantle structure of a major continental strike-slip fault, we present a high-resolution teleseismic tomography of the North Anatolian Fault Zone (NAFZ) in Turkey. Our results highlight the presence of a relatively high velocity body between the two branches of the fault and significant along-strike variations in the NAFZ velocity structure over distances of ~20 km. We interpret these findings as evidence of laterally variable strain focussing caused by preexisting heterogeneity. Low velocities observed in the crust and upper mantle beneath the NAFZ support the presence of a narrow shear zone widening in the upper mantle, where we constrain its width to be ~50 km.Major funding was provided by the UK Natural Environment Research Council (NERC) under grant NE/I028017/1. Equipment was provided and supported by the NERC Geophysical Equipment Facility (SEIS-UK). This project is also supported by Bogaziçi University Scientific ˘ Research Projects (BAP) under grant 6922 and Turkish State Planning Organization (DPT) under the TAM project, number 2007K120610

Recurrent Ascending Colon Cancer Manifesting as Inferior Vena cava Thrombus

We report an extremely rare case of recurrent ascending colon cancer manifesting as inferior vena cava (IVC) thrombus. A 77-year-old woman previously diagnosed with ascending colon cancer underwent right hemicolectomy with lymph node dissection. Though the tumor invaded the retroperitoneum and involved the right ovarian artery and vein, curative operation was performed. The patient took 5-FU p.o. Two and a half years later, tumor thrombus in the IVC extending into the right atrium was incidentally found and diagnosed as recurrence of colon cancer by biopsy. RF-induced hyperthermia using 5-FU and CDDP i.v. was immediately performed, but she died after 6 months because of multiple liver and pulmonary metastases. In treating colon cancers invading the retroperitoneum, it should be recalled that some cases recur as tumor thrombus in the IVC and that close follow-up is therefore necessary

Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma

Background: Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. Methods: A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. Results: NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. Conclusion: The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors. © 2014 The International Society of Dermatology

Effect of alkali treatment of lower concentrations on the structure and tensile properties of Pakistan’s coarse cotton fibre

Cotton fibres of high Micronaire values are known to have inferior spinning performance. Either reduction of fibres’ fineness or increase in tensile strength is generally expected to improve the spinnability of fibres. In this piece of research, the effects of alkali treatment at lower concentrations (0.75–2.25M) and higher temperatures (70–100 °C) on the cross-section of cotton fibre and on the tensile strength have been investigated. Observations were made using scanning electron microscopy (SEM) and single fibre tensile strength testing. It was found that the roundness of the fibre cross section was improved and the tensile strength of the fibres also increased after treatment with alkali at lower concentration (0.75 M) and relatively lower temperature (70 °C). It is proposed that such changes occurred due to possible cellulose dissolution/transformations. It was thus concluded that the alkali treatment of cotton fibres at lower concentrations (0.75 M) and 70 °C for a shorter period of time (45 mins) could lead to improvement in tensile strength and roundness of fibre cross-section, thereby improving micronaire