8 research outputs found
Pan-cancer experimental characteristic of human transcriptional patterns connected with telomerase reverse transcriptase (TERT) gene expression status
The TERT gene encodes the reverse transcriptase subunit of telomerase and is normally transcriptionally suppressed in differentiated human cells but reactivated in cancers where its expression is frequently associated with poor survival prognosis. Here we experimentally assessed the RNA sequencing expression patterns associated with TERT transcription in 1039 human cancer samples of 27 tumor types. We observed a bimodal distribution of TERT expression where ∼27% of cancer samples did not express TERT and the rest showed a bell-shaped distribution. Expression of TERT strongly correlated with 1443 human genes including 103 encoding transcriptional factor proteins. Comparison of TERT- positive and negative cancers showed the differential activation of 496 genes and 1975 molecular pathways. Therein, 32/38 (84%) of DNA repair pathways were hyperactivated in TERT+ cancers which was also connected with accelerated replication, transcription, translation, and cell cycle progression. In contrast, the level of 40 positive cell cycle regulator proteins and a set of epithelial-to-mesenchymal transition pathways was specific for the TERT- group suggesting different proliferation strategies for both groups of cancer. Our pilot study showed that the TERT+ group had ∼13% of cancers with C228T or C250T mutated TERT promoter. However, the presence of promoter mutations was not associated with greater TERT expression compared with other TERT+ cancers, suggesting parallel mechanisms of its transcriptional activation in cancers. In addition, we detected a decreased expression of L1 retrotransposons in the TERT+ group, and further decreased L1 expression in promoter mutated TERT+ cancers. TERT expression was correlated with 17 genes encoding molecular targets of cancer therapeutics and may relate to differential survival patterns of TERT- positive and negative cancers
Применение данных компьютерной томографии в диагностике и лечении пациентов с аномалиями зубочелюстной системы, сопровождающимися сужением верхней челюсти
The Purpose. Create an algorithm of using computed tomographydata in patients with malocclusion, accompanied by the narrowing of the maxilla. Create description CT data protocols. Materials and methods. Were examined 20 patients with malocclusion, accompanied by the narrowing of the maxilla. All CT examinations were performed on Toshiba Aquilion ONE, 320 before treatment and 6 months after rapid maxilla expansion. Description CT protocols of these studies were developed. Results. After rapid maxilla expansion it was found that the maximum expansion of the maxilla was at the level of canines, then at the level of premolars, first molars, second molars. 6 months after distraction the density of bone regenerate in the projection of the median palatal suture was estimated. When the distraction was 1-4 mm regenerate bone density ranged 520-890 HU. When distraction was 4-9 mm density varied 320-614 HU. These indicators gave the opportunity to plan further treatment in this group of patients. Conclusion. Computed tomography is an indispensable study in patients with malocclusion, accompanied by the narrowing of the maxilla, and should be performed in all patients before and after rapid maxilla expansion.Цель исследования: разработать алгоритм КТ- обследования пациентов с аномалиями зубочелюстной системы, сопровождающимися сужением верхней челюсти, а также разработать протоколы описания данных КТ у этой группы пациентов. Материал и методы. Обследовано 20 пациентов с аномалиями зубочелюстной системы, сопровождающимися сужением верхней челюсти. Всем пациентам КТ-исследования были выполнены на компьютерном томографе Toshiba Aquilion ONE, количество рядов детекторов 320, до начала лечения и через 6 мес после хирургического расширения верхней челюсти. Были разработаны протоколы описания данных исследований. Результаты. После хирургического расширения верхней челюсти на основании оцениваемых параметров было получено, что максимальное расширение верхней челюсти приходится на уровне клыков, далее по степени уменьшения на уровне премоляров, первых моляров, вторых моляров. При определении плотности костного регенерата в проекции срединного небного шва было установлено, что спустя 6 мес после дистракции от 1 до 4 мм плотность костного регенерата составляла от 520 до 890 ед.К При дистракции от 4 до 9 мм плотность варьировала от 320 до 614 ед.К Эти показатели давали возможность спланировать дальнейшее лечение у данной группы пациентов. Выводы. КТ является незаменимым методом исследования у пациентов с аномалиями зубочелюстной системы, сопровождающимися сужением верхней челюсти, и должна проводиться всем пациентам до и после проведения хирургического расширения верхней челюсти
Socket Preservation During Preimplantation Period: Effi cacy of Osteoplastic Material Application Using Cone Beam Computed Tomography
Aim. To analyse the effi ciency of osteoplastic material application in order to reduce the resorption level after tooth extraction in the preimplantation period according to the data of cone beam computed tomography.Materials and methods. The study involved 80 patients who were divided into 4 equal groups depending on the preservation material used. The fi rst group was treated with Cerabone (Botiss, Germany) xenomaterial based on natural bovine bone. Plasma enriched with PRGF growth factors obtained by the BTI Endoret (Spain) technology was used for the patients of the second group. The third group consisted of patients who underwent a socket preservation of the extracted tooth with a powdered autologous dentin matrix (ADM) obtained from their own tooth. In the fourth group, bone-plastic material based on hydroxyapatite with Collapan-L lincomycin hydrochloride (Intermedapatit, Russia) was used to prevent socket resorption. All patients had a cone beam computed tomography of the maxillofacial region before the extraction and 3 months after the preservation in order to evaluate the level of bone resorption. After the installation of dental implants, a comparative assessment of the bone resorption level in the vertical and horizontal directions before tooth extraction and in the preimplantation period was carried out.Results. The smallest level of vertical bone resorption after socket preservation was observed in group 1 (Cerabone) and group 3 (ADM). The median value of the socket resorption level in group 1 was 0.7 mm (8.54 %) in the vertical direction and 0.5 mm (9.45 %) in horizontal measurement as compared to the level of bone tissue before tooth extraction. Similar indicators were observed in the group using an autologous dentin matrix. The vertical decrease in the socket bone tissue was 0.61 mm (7.75 %), horizontal — 0.51 mm (6.2 %). The level of bone resorption was signifi cantly higher using two other materials.Conclusions. The use of three-dimensional radiation research methods allows a comprehensive assessment of the bone tissue volume to be carried out, which in turn determines the choice of the dental implant size, the need for further bone-plastic surgery to increase the width/height of the alveolar ridge. The use of cone beam computed tomography showed that the most optimal results can be obtained by introducing Cerabone material into the socket of the extracted tooth, as well as using the innovative method of preservation with the patient’s own powdered tooth (ADM)
Profiling at mRNA, protein and metabolite level reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2-I- mice
PEPT2 is an integral membrane protein in the apical membrane of renal epithelial cells that operates as a rheogenic transporter for di- and tripeptides and structurally related drugs. Its prime role is thought to be the reabsorption of filtered di- and tripeptides contributing to amino acid homeostasis. To elucidate the role of PEPT2 in renal amino acid metabolism we submitted kidney tissues of wild-type and a Pept2(-/-) mouse line to a comprehensive transcriptome, proteome and metabolome profiling and analyzed urinary amino acids and dipeptides. cDNA microarray analysis identified 147 differentially expressed transcripts in transporter-deficient animals, and proteome analysis by 2D-PAGE and MALDI-TOF-MS identified 37 differentially expressed proteins. Metabolite profiling by GC-MS revealed predominantly altered concentrations of amino acids and derivatives. Urinary excretion of amino acids demonstrated increased glycine and cysteine/cystine concentrations and dipeptides in urine were assessed by amino acid analysis of urine samples before and after in vitro dipeptidase digestion. Dipeptides constituted a noticeable fraction of urinary amino acids in Pept2(-/-) animals, only, and dipeptide-bound glycine and cystine were selectively increased in Pept2(-/-) urine samples. These findings were confirmed by a drastically increased excretion of cysteinylglycine (cys-gly). Urinary loss of cys-gly together with lower concentrations of cysteine, glycine, and oxoproline in kidney tissue and altered expression of mRNA and proteins involved in glutathione (GSH) metabolism suggests that PEPT2 is predominantly a system for reabsorption of cys-gly originating from GSH break-down, thus contributing to resynthesis of GSH
Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue of Pept2
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Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers.
Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived healthy normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact differential expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice
Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers
Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived “healthy” normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min – 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact “differential” expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice